Showing papers in "Immunopharmacology and Immunotoxicology in 2009"
TL;DR: In chronic inflammatory diseases, peroxynitrite formed by phagocytic cells may cause damage to DNA, generating neoepitopes leading to the production of autoantibodies in various autoimmune disorders such as systemic lupus erythematosus (SLE).
Abstract: Reactive nitrogen species include nitric oxide (.NO), peroxynitrite (ONOO(-)) and nitrogen dioxide radical (NO2*). Peroxynitrite is a reactive oxidant, produced from nitric oxide (*NO) and superoxide anion (O(2*-), that reacts with a variety of biological macromolecules. It is produced in the body in response to physiological stress and environmental toxins. It is a potent trigger of oxidative protein and DNA damage-including DNA strand breakage and base modification. It activates the nuclear enzyme poly-ADP ribose polymerase (PARP) resulting in energy depletion and apoptosis/necrosis of cells. Peroxynitrite generation is a crucial pathological mechanism in stroke, diabetes, inflammation, neurodegeneration, cancer, etc. Peroxynitrite modified DNA may also lead to the generation of autoantibodies in various autoimmune disorders such as systemic lupus erythematosus (SLE). In chronic inflammatory diseases, peroxynitrite formed by phagocytic cells may cause damage to DNA, generating neoepitopes leading to the production of autoantibodies. Hence, understanding the pathophysiology of peroxynitrite could lead to important therapeutic interventions.
103 citations
TL;DR: The therapeutic efficacy of antioxidants in MS disease is clarified to clarify the effect of treatments with such compounds in patients with MS.
Abstract: Reactive oxygen species (ROS) play an important role in various events underlying multiple sclerosis pathology. In the initial phase of lesion formation, ROS are known to mediate the transendothelial migration of monocytes and induce a dysfunction in the blood-brain barrier. Although the pathogenesis of MS is not completely understood, various studies suggest that reactive oxygen species contribute to the formation and persistence of multiple sclerosis lesions by acting on distinct pathological processes. The detrimental effects of ROS in the central nervous system are endowed with a protective mechanism consisting of enzymatic and non-enzymatic antioxidant. Antioxidant therapy may therefore represent an attractive treatment of MS. Several studies have shown that antioxidant therapy is beneficial in vitro and in vivo in animal models for MS. Since oxidative damage has been known to be involved in inflammatory and autoimmune-mediated tissue destruction in which, modulation of oxygen free radical production represents a new approach to the treatment of inflammatory and autoimmune diseases. Several experimental studies have been performed to see whether dietary intake of several antioxidants can prevent and or reduce the progression of EAE or not. Although a few antioxidants showed some efficacy in these studies, little information is available on the effect of treatments with such compounds in patients with MS. In this review, our aim is to clarify the therapeutic efficacy of antioxidants in MS disease.
85 citations
TL;DR: Punarnavine significantly reduced the LPS induced elevated levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 in mice and showed enhanced proliferation of splenocytes, thymocytes and bone marrow cells both in the presence and absence of specific mitogens in vitro and in vivo.
Abstract: The effect of Punarnavine on the immune system was studied using Balb/c mice. Intraperitoneal administration of Punarnavine (40 mg/kg body weight) was found to enhance the total WBC count on 6(th) day. Bone marrow cellularity and number of alpha-esterase positive cells were also increased by the administration of Punarnavine. Treatment of Punarnavine along with the antigen, sheep red blood cells (SRBC), produced an enhancement in the circulating antibody titer and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC was obtained on the 6(th) day. Punarnavine also showed enhanced proliferation of splenocytes, thymocytes and bone marrow cells both in the presence and absence of specific mitogens in vitro and in vivo. More over administration of Punarnavine significantly reduced the LPS induced elevated levels of proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 in mice. These results indicate the immunomodulatory activity of Punarnavine.
82 citations
TL;DR: Vernonia cinerea extract significantly inhibited carrageenan induced inflammation, compared with control models and down regulation of pro-inflammatory cytokine level and gene expression were also support the above result.
Abstract: In this study, we evaluated the anti-oxidant and anti-inflammatory activities of the medicinal plant, Vernonia cinerea L (Asteraceae) using in vitro as well as in vivo models. Methanolic extract of Vernonia cinerea was found to scavenge the hydroxyl radical generated by Fenton reaction (IC(50)130 microg/ml), Superoxide generated by photo reduction of riboflavin (IC(50)190 microg/ml) and inhibited lipid peroxidation significantly (IC(50)130.5 microg/ml). The drug also scavenged nitric oxide (IC(50)210 microg/ml). Intraperitoneal administration of Vernonia cinerea was found to inhibit the PMA induced Superoxide generation in mice peritoneal macrophages. The administration of Vernonia cinerea to mice significantly increased the levels of catalase, superoxide dismutase, glutathione, glutathione peroxidase and glutathione-S transferase in blood and liver, whereas lipid peroxidation activity was significantly decreased. It was also found that Vernonia cinerea extract significantly inhibited carrageenan induced inflammation, compared with control models. Down regulation of pro-inflammatory cytokine level and gene expression were also support the above result.
73 citations
TL;DR: The structure, genetic polymorphisms, expression and biological functions of CR1, the receptor for C3b/C4bcomplement peptides, have been brought forth for the first time.
Abstract: The complement system is comprised of soluble and cell surface associated proteins that recognize exogenous, altered, or potentially harmful endogenous ligands. In recent years, the complement system—particularly component C3 and its receptors—have been demonstrated to be a key link between innate and adaptive immunity. Complement receptor type 1 (CR1), the receptor for C3b/C4bcomplement peptides, has emerged as a molecule of immense interest in gaining insight to the susceptibility, pathophysiology, diagnosis, prognosis and therapy of such diseases. In this review, we wish to briefly bring forth the structure, genetic polymorphisms, expression and biological functions of CR1.
69 citations
TL;DR: In vitro and in vivo results indicated that GC was a strong immunological stimulant and its non-toxic nature and immunological activity make GC a potential immunoadjuvant for treatment of metastatic tumors.
Abstract: Chitosan is capable of stimulating immune responses. However, because chitosan is not water soluble, it has limited biological applications. By attaching galactose molecules to the chitosan molecules, a new water-soluble compound, glycated chitosan (GC), was synthesized. GC was designed for immune stimulations in combination with phototherapies in the treatment of metastatic tumors. To investigate the possible toxicity of GC, cultures of normal and tumor cells were incubated with GC of different concentrations and the cell viabilities were determined. For in vivo studies, GC solution was fed or injected to animals and its toxicity was determined through observations of animals and histological examinations of vital organs. No toxic effects of GC were observed in cultured cells or in animal studies. In addition, the immunological effect of GC was investigated through its stimulation of TNFα secretion by macrophages in vitro. In vivo studies showed enhancement of the survival of laser immunotherapy-treated ...
65 citations
TL;DR: This review has made an honest attempt to analyze various biological activities of gemfibrozil and associated mechanisms that may help to consider this drug for different human disorders as primary or adjunct therapy.
Abstract: Gemfibrozil is long known for its ability to reduce the level of triglycerides in the blood circulation and to decrease the risk of hyperlipidemia. However, a number of recent studies reveal that apart from its lipid-lowering effects, gemfibrozil can also regulate many other signaling pathways responsible for inflammation, switching of T-helper cells, cell-to-cell contact, migration, and oxidative stress. In this review, we have made an honest attempt to analyze various biological activities of gemfibrozil and associated mechanisms that may help to consider this drug for different human disorders as primary or adjunct therapy.
64 citations
TL;DR: Investigation of the effects of increasing concentrations of Lactobacillus rhamnosus strain GG (L. GG) homogenate on cell growth and proliferation in neoplasms originating from different gastrointestinal tracts suggests that cytoplasm extracts could be the responsible for L. GG action on proliferation in these two cell lines from gastric and colonic neoplasm.
Abstract: Previous in vitro and in vivo studies have suggested that lactobacilli can exert antiproliferative effects on the gastrointestinal epithelium. However, their role in affecting the cellular proliferative mechanisms is not completely clear. The aim of this study was to investigate the effects of increasing concentrations of Lactobacillus rhamnosus strain GG (L. GG) homogenate on cell growth and proliferation (by MTT, [3H]-thymidine incorporation and polyamine biosynthesis) in neoplasms originating from different gastrointestinal tracts. Thus, HGC-27 human gastric cancer cells and DLD-1 human colonic adenocarcinoma cells were evaluated. Besides, in order to verify which bacterial fraction was involved in the antiproliferative effects, the cytoplasm and cell wall extracts were tested separately. Gastric HGC-27 and colonic DLD-1 cells showed significant differences in their proliferative behavior, in particular in their polyamine profile and biosynthesis. Notwithstanding, one and the other proved to be sensitive to the growth inhibition by the highest concentrations of bacterial homogenate. Both HGC-27 and DLD-1 cells were resistant to the bacterial cell wall fractions, whereas increasing cytoplasm fraction concentrations induced an evident antiproliferative effect. These data suggest that cytoplasm extracts could be the responsible for L. GG action on proliferation in these two cell lines from gastric and colonic neoplasms.
64 citations
TL;DR: A review of Toll-like receptors and their ligands and their use in clinical trials as vaccine adjuvants, and to treat allergy, cancer and infectious diseases, and potential drawbacks related to their potential use as prophylactic and/or therapeutic agents are discussed.
Abstract: Toll-like receptors (TLR) and their ligands are one of the main players in the initiation of innate immunity which precedes, and is required, for the establishment of adaptive immunity. Manipulating the immune response by using TLR agonists or antagonists might be of therapeutic and/or prophylactic value. This review covers; 1-TLR. their natural ligands and ligand - TLR signaling events, 2-TLR againsts and their use in clinical trials as vaccine adjuvants, and to treat allergy, cancer and infectious diseases, 3-TLR antagonists and their use in clinical trials to treat septic shock and autoimmune diseases. Potential drawbacks related to their potential use as prophylactic and/or therapeutic agents are discussed.
57 citations
TL;DR: It is demonstrated that XN has profound immunosuppressive effects on T cell proliferation, development of IL-2 activated killer (LAK) cells, cytotoxic T lymphocytes (CTLs), and production of Th1 cytokines (IL-2, IFN-γ and TNF-α).
Abstract: Xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupus L.) and beer, exhibits anti-inflammatory, antioxidant and antiproliferative activity, but has not been studied for effects on T cell-mediated immune responses. Here we demonstrate that XN has profound immunosuppressive effects on T cell proliferation, development of IL-2 activated killer (LAK) cells, cytotoxic T lymphocytes (CTLs), and production of Th1 cytokines (IL-2, IFN-γ and TNF-α). The suppression of these cell-mediated immune responses by XN was at, least in part, due to the inhibition of nuclear factor kappa B (NF-κB) transcription factor through suppression of phosphorylation of IκBα, an inhibitor of NF-κB.
49 citations
TL;DR: It is suggested that dietary supplementation with ABP to weaned piglets enhances cellular and humoral immune responses, and ABP addition to culture medium also increases the proliferation activity and cytokine production of lymphocytes cultured in vitro, which indicate that dietary supplements with the herbal polysaccharide may offer an effective alternative to antibiotics for weaned Piglets.
Abstract: The acquired immunity is underdeveloped at 3-4 weeks of age when piglets are usually weaned on commercial farms, and weaning is associated with compromised immunity. Dietary supplementation with immunomodulatory phytochemicals may enhance immune responses in the weaned piglets. This study is conducted to investigate the effects of dietary supplemental achyranthes bidentata polysaccharide (ABP) on proliferation activity of lymphocytes, and production of antibodies, complements and cytokines in weaned piglets. Results showed that lymphocyte proliferation activity in piglets fed diets supplementing with 1000 and 1500 mg/kg ABP increased (P < 0.05) on days 14 and 28 compared with the non-additive piglets, as well as serum contents of IgG, IgA, IgM, C(3), C(4), IL (interleukin)-2 and IFN (interferon)-gamma. The ABP had dose-dependent immunomodulatory activity and the dose of 1500 mg/kg presented the strongest stimulating activity in vivo. In addition, the ABP increased (P < 0.05) the proliferation activity and production of IL-2 and IFN-gamma of cultured lymphocytes in dose- or time-dependent manner. The proliferation activity of peripheral T cells and splenic lymphocytes in 400 microg/ml of ABP group arrived at their peak values, as well as the production of IL-2 and IFN-gamma at 72 and 12 h after the treatment, respectively. Collectively, these findings suggested that dietary supplementation with ABP to weaned piglets enhances cellular and humoral immune responses, and ABP addition to culture medium also increases the proliferation activity and cytokine production of lymphocytes cultured in vitro, which indicate that dietary supplementation with the herbal polysaccharide may offer an effective alternative to antibiotics for weaned piglets.
TL;DR: There is evidence that an infectious insult could be a likely trigger of SIDS in some infants, and the causal link between infection and SIDS is not conclusive.
Abstract: Sudden Infant Death Syndrome (SIDS) is the most common cause of post-neonatal mortality in the developed world. The exact cause of SIDS is likely to be multifactorial involving a critical developmental period, a vulnerable infant, and one or more triggers. Many SIDS infants have a history of viral illness preceding death. Prone sleep position, one of the leading risk factors, can increase airway temperature, as well as stimulate bacterial colonization and bacterial toxin production. Markers of infection and inflammation are often found on autopsy along with microbial isolates. Although the causal link between infection and SIDS is not conclusive, there is evidence that an infectious insult could be a likely trigger of SIDS in some infants.
TL;DR: In Peyer’s patches, SIgA-based immune complexes are internalized by underlying antigen-presenting cells, leaving the antigen with masked epitopes, a form that limits the risk of overwhelming the local immune protection system with danger signals.
Abstract: At mucosal surfaces, secretory IgA (SIgA) antibodies serve as the first line of defense against microorganisms through a mechanism called immune exclusion that prevents interaction of neutralized antigens with the epithelium. In addition, SIgA plays a role in the immune balance of the epithelial barrier through selective adhesion to M cells in intestinal Peyer's patches. This mediates the transepithelial retro-transport of the antibody and associated antigens from the intestinal lumen to underlying gut-associated organized lymphoid tissue. In Peyer's patches, SIgA-based immune complexes are internalized by underlying antigen-presenting cells, leaving the antigen with masked epitopes, a form that limits the risk of overwhelming the local immune protection system with danger signals. This translates into the onset of mucosal and systemic responses associated with production of anti-inflammatory cytokines and limited activation of antigen-presenting cells. In the gastrointestinal tract, SIgA exhibits thus properties of a neutralizing agent (immune exclusion) and of an immunopotentiator inducing effector immune responses in a noninflammatory context favorable to preserve local homeostasis.
TL;DR: The data suggest that all seven active ingredients of PD can effectively reduce inflammatory response, thus relieving intestinal dysfunction via multiple pathways.
Abstract: The aim of the research was to investigate the anti-inflammatory mechanism of Pulsatillae Decoction (PD), the levels of interleukin (IL)-6, IL-8, E-selectin, and thromboxane B(2) (TXB(2)) secreted by cultured rat intestinal microvascular endothelial cells (RIMECs) were determined after treatment with its active ingredients, namely anemoside B4, anemonin, berberine, jatrorrhizine, palmatine, aesculin, and esculetin. RIMECs were challenged with 1 microg/mL lipopolysaccharide (LPS) for 3 h, and then treated with each of the seven ingredients at three concentrations (1, 5 and 10 microg/mL) for 24 h. The results revealed that anemonin, aesculin and esculetin inhibited the production of IL-6, aesculin and esculetin inhibited the secretion of IL-8, anemoside B4, berberine and jatrorrhizine downregulated E-selectin expression, anemonin, berberine, jatrorrhizine and palmatine decreased the content of TXB(2). All these changes were significant. Taken together, the data suggest that all seven active ingredients of PD can effectively reduce inflammatory response, thus relieving intestinal dysfunction via multiple pathways.
TL;DR: Results clearly demonstrated that propolis may be effective in the relief of symptoms of allergic rhinitis through inhibition of histamine release.
Abstract: We studied the effect of Brazilian propolis on sneezing and nasal rubbing in experimental allergic rhinitis of mice. A single administration of propolis caused no significant effect on both antigen-induced nasal rubbing and sneezing at a dose of 1000 mg/kg, but a significant inhibition was observed after repeated administration for 2 weeks at this dose. Propolis caused no significant inhibitory effect on the production of total IgE level after repeated administration of 1000 mg/kg. The drug also caused no significant inhibition of histamine-induced nasal rubbing and sneezing at a dose of 1000 mg/kg. On the other hand, propolis significantly inhibited histamine release from rat mast cells induced by antigen and compound 48/80 at a concentration of more than 10 μg/ml. These results clearly demonstrated that propolis may be effective in the relief of symptoms of allergic rhinitis through inhibition of histamine release.
TL;DR: Serum galectin-3 might represent a useful biomarker to evaluate colon cancer transformation and, together with its ligand 90K, could contribute to the characterization of colon cancer.
Abstract: Galectin-3 is an endogenous lectin that binds glycan epitopes of cell membrane and some extracellular glycoproteins such as integrins and laminin. Galectin-3 is involved in several biological activities including regulation of cellular cycle, modulation of adhesion and tumor progression and metastasis. 90K/Mac-2BP glycoprotein is also a serum galectin-3 ligand. 90K is able to modulate the immune reaction against tumors and viruses and its level increases in sera of several neoplastic diseases. In our study, we have evaluated levels of both glycoproteins in sera of non metastatic colon cancer patients. Interestingly, galectin-3 ranged higher in cancer patients than in controls (p<0.0001), particularly in more differentiated tumors (p<0.04). Moreover, 90K mean values ranged higher in right-side than in left-side colon cancer. In conclusion, serum galectin3 might represent a useful biomarker to evaluate colon cancer transformation and, together with its ligand 90K, could contribute to the characterization of colon cancer.
TL;DR: Results indicate that MW may be helpful in regulating inflammatory diseases, possibly by inhibiting NF-κB activation.
Abstract: Motherwort (MW), a Korean folk medicine, has been applied to treat inflammatory disease. However, its effect on inflammatory cytokine release from mast cells is not well known. We investigated the anti- inflammatory effect of MW on the secretion of inflammatory cytokine such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 and IL-8 in human mast cell line (HMC-1). MW was treated in vitro before activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187. MW had no cytotoxic effects on HMC-1 cell viability. MW (1 mg/ml) inhibited PMA plus A23187-stimulated gene expression and production of TNF-alpha, IL-6, and IL-8. Stimulation with PMA plus A23187 induced NF-kappaB activation in HMC-1 cells, which was inhibited by MW (1 mg/ml). MW inhibited secretion of TNF-alpha, IL-6, and IL-8 possibly by inhibiting NF-kappaB activation. These results indicate that MW may be helpful in regulating inflammatory diseases.
TL;DR: The IL10 gene transcription did not associate with enhancement of c-Jun, RelA and FOXP3 gene expression and strictly depended on the JNK and p38 MAPKs activation in stimulated human monocytes.
Abstract: Interleukin-10 is the most important anti-inflammatory cytokine that controls the progress of the immune response. The molecular mechanisms driving the IL10 gene regulation are not well understood. To gain insight into this process we studied the IL-10 expression on mRNA and protein levels, together with c-Jun, FOXP3 and RelA transcription factors gene expression in human monocytes. We investigated also, the involvement of JNK and p38 transduction pathways in IL-10, c-Jun, FOXP3 and RelA gene expression. The quantity determination of IL-10 was performed by ELISA. qRT-PCR was performed for the detection of mRNA transcripts. The pharmacological inhibitors SP600125 and SB202190 were used to explore JNK and p38 MAPKs involvement in IL10, c-Jun, FOXP3 and RelA gene expression. The measurement of IL-10 mRNA synthesis, triggered by lipopolysaccharide (LPS) or C3 binding glycoprotein (C3bgp) showed that stimulation with both inducers led to similar high level of IL-10 mRNA synthesis, whereas C3bgp was the stronger inducer of IL-10 production than LPS. JNK and p38 inhibition significantly decreased IL-10 expression in stimulated cells. C3bgp and LPS induced comparatively low expression of FOXP3, RelA and c-Jun mRNA in monocytes. The inhibition of p38 MAPK in stimulated monocytes resulted in significant enhancement of c-Jun mRNA synthesis suggesting the functional relation between p38 MAPK and c-Jun gene expression. We concluded that the IL10 gene transcription did not associate with enhancement of c-Jun, RelA and FOXP3 gene expression and strictly depended on the JNK and p38 MAPKs activation in stimulated human monocytes.
TL;DR: The levels of ROS in cystic and follicular fluid were evaluated to establish their involvement in the etiopathogenesis of Cystic Ovarian Follicle (COF) in dairy cows, suggesting that an alteration of the cascade responsible for ROS production may be implicated in the complex etipathogenic of COF.
Abstract: Ovulation is compared to an acute inflammatory process during which vasoactive agents, prostanoids, leukotrienes and Reactive Oxygen Species (ROS) develop. The aim of this study was to evaluate the levels of ROS in cystic and follicular fluid, in order to establish their involvement in the etiopathogenesis of Cystic Ovarian Follicle (COF) in dairy cows. The study was conducted in 30 healthy cows (group C) and 30 cows affected by COF (group COF). The fluid of follicular cysts and of preovulatory follicles was drawn by means of ultrasound guided aspiration from the cows of both groups. The fluid obtained was analyzed by a photometric analytical system to detect ROS level. ROS concentration was statistically lower in the cystic fluid than in the follicular one (62.4 +/- 13.36 U.Carr vs. 84.89 +/- 26.99 U.Carr) (p<0.05), thus suggesting that an alteration of the cascade responsible for ROS production may be implicated in the complex etipathogenesis of COF.
TL;DR: The ability of Anacardium occidentale bark extract to neutralize enzymatic as well as pharmacological effects induced by Vipera russelii venom is studied to find a rich source of potential inhibitors of hydrolytic enzymes involved in several physiopathological diseases.
Abstract: Snakebites in rural areas of tropical and subtropical regions are commonly treated with medicinal plants. In this report, we have studied the ability of Anacardium occidentale bark extract to neutralize enzymatic as well as pharmacological effects induced by Vipera russelii venom. The extract neutralized the viper venom hydrolytic enzymes such as phospholipase, protease, and hyaluronidase in a dose dependent manner. These enzymes are responsible for both local effects of envenomation such as local tissue damage, inflammation and myonecrosis, and systemic effects including dysfunction of vital organs and alteration in the coagulation components. In addition, extract neutralized the pharmacological effects such as edema, hemorrhage, and myotoxic effects including lethality, induced by venom. Since, it inhibits both hydrolytic enzymes and pharmacological effects; it may be used as an alternative treatment to serum therapy and, in addition, as a rich source of potential inhibitors of hydrolytic enzymes involv...
TL;DR: Polyphenols from the extracts of Areca catechu L. and Quercus infectoria Oliv inhibited the hemorrhagic activity of CR venom and the dermonecrotic activity of NK venom by in vivo tests, implying the therapeutic potential of plant polyphenols against necrosis in snakebite victims.
Abstract: Polyphenols from the extracts of Areca catechu L. and Quercus infectoria Oliv. inhibited phospholipase A2, proteases, hyaluronidase and L-amino acid oxidase of Naja naja kaouthia Lesson (NK) and Calloselasma rhodostoma Kuhl (CR) venoms by in vitro tests. Both extracts inhibited the hemorrhagic activity of CR venom and the dermonecrotic activity of NK venom by in vivo tests. The inhibitory activity of plant polyphenols against local tissue necrosis induced by snake venoms may be caused by inhibition of inflammatory reactions, hemorrhage, and necrosis. The result implies the therapeutic potential of plant polyphenols against necrosis in snakebite victims.
TL;DR: The role of oxygen, pH, lactate and cytokines of tumor micro-environment associated with physical exercise-dependent alteration in the growth properties of tumor cells is investigated to explore their contribution in modulation of tumor.
Abstract: Recently, we reported that treadmill exercise renders survival benefits in a murine tumor model of a transplantable lymphoma of spontaneous origin, designated as Dalton’s lymphoma (DL), owing to an augmented apoptosis of tumor cells. However, the underlying the mechanisms of the same remained unclear with respect to the role alterations if any in the components of tumor microenvironment following physical exercise. Therefore, in the present we investigated the role of oxygen, pH, lactate and cytokines of tumor micro-environment associated with physical exercise-dependent alteration in the growth properties of tumor cells to explore their contribution in modulation of tumor. Physical exercise of tumor-bearing host resulted in a decreased angiogenesis in the vicinity of tumor. This was also found to be accompanied by a decrease in erythrocyte count and increase in the level of oxygen while the content of lactate showed a concomitant decrease in the tumor microenvironment along with normalization of pH. More...
TL;DR: Physalis peruviana’s anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which directly or indirectly “blocks” their ability to secrete soluble proinflammatory mediators.
Abstract: The study of plants used in traditional medicine has drawn the attention of researchers as an alternative in the development of new therapeutics agents, such as the American Solanaceae Physalis peruviana, which has significant anti-inflammatory activity. The Physalis peruviana anti-inflammatory effect of ethanol or ether calyces extracts on the phagocytic process was assessed by using an in vitro phagocytosis model (Leishmania panamensis infection to murine macrophages). The Physalis peruviana extracts do not inhibit microorganism internalization and have no parasiticide effect. Most ET and EP extracts negatively affected the parasite’s invasion of macrophages (Infected cells increased.). This observation might result from a down-regulation of the macrophage’s microbicide ability associated with a selective reduction of proinflammatory cytokines levels. Physalis peruviana’s anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which di...
TL;DR: CO and bilirubin can inhibit DOX-induced apoptosis in H9c2 cardiomyocytes, implying that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by protecting againstCardiomyocyte death.
Abstract: The clinical utility of anthracycline anticancer agents, especially doxorubicin (DOX), is limited by progressive toxic cardiomyopathy linked to cardiomyocyte apoptosis. This study examined the protective effects of CO and bilirubin on DOX-induced cardiomyocyte toxicity. In vitro, DOX significantly decreased the viability of H9c2 cells and increased apoptotic features, such as changes in nuclear morphology and caspase protease activation. CO and bilirubin significantly inhibited DOX-induced cell death and caspase-3 activation, which may be explained by increased Bcl-2 expression and inhibition of Bax expression. CO and bilirubin up-regulated the heme oxygenase-1 (HO-1), which was required for the protective effect of CO, and a single bilirubin treatment increased DOX-induced apoptosis in H9c2 cells. The inhibition of HO-1 with ZnPP resulted in a striking increase in apoptosis in the CO, bilirubin, and DOX-treated cells. Furthermore, HO-1 overexpression increased resistance against DOX-induced cytotoxicity in H9c2 cells. In conclusion, CO and bilirubin can inhibit DOX-induced apoptosis in H9c2 cardiomyocytes. These findings imply that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by protecting against cardiomyocyte death.
TL;DR: Findings show a potential for the combination of STAT3 inhibition in tumor and TLR4 induced DC activation in increasing the efficacy of cancer immunotherapy.
Abstract: The efficiency of cancer immunotherapy strategies is hampered by the existence of an intra-tumoral immunosuppressive environment involving tolerogenic dendritic cells (DCs) and regulatory T (T(reg)) cells. Hyperactivation of STAT3 in tumor is implicated in the generation of this immunosuppressive environment. The purpose of this study was to test whether simultaneous inhibition of STAT3 in tumor and TLR4 ligand-induced activation of DCs can modulate tumor-induced immunosuppression. For this purpose, the effects of a TLR4 ligand, 7-acyl lipid A, delivered by poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) to DCs on the activity of DCs and T(reg) cells was evaluated in vitro. In addition the immunomodulatory and anticancer effects of 7-acyl lipid A PLGA-NPs in combination with a STAT3 inhibitory agent, JSI-124, in a B16 mouse melanoma model was explored, in vivo. PLGA-NP delivery of 7-acyl lipid A to DCs reduced the suppressive effects of T(reg) cells on T cells in vitro. Besides, daily Intra-tumoral co-administration of 7-acyl lipid A PLGA-NPs and JSI-124 in C57BL/6 mice bearing B16-F10 tumor for 8 days resulted in a significant increase in the percentage of tumor infiltrated T cells as compared with control group that received PBS and monotherapy groups. The average tumor volume in the tumor-bearing mice that received JSI-124 plus 7-acyl lipid A PLGA-NPs combination therapy was found to be significantly lower than that in PBS and monotherapy groups. Our findings show a potential for the combination of STAT3 inhibition in tumor and TLR4 induced DC activation in increasing the efficacy of cancer immunotherapy.
TL;DR: The inhibitory effect of H2O2 was related to the activation of the ERK and P38 pathway, NO production and apoptosis, and drugs capable of producing an increase in H 2O2 levels could be used in cancer.
Abstract: BW 5147 (murine lymphoma cell line). We analyzed the effect of H2O2 in cell proliferation testing nitric oxide and apoptosis. Enzymes involved in the regulation of H2O2 levels as superoxide dismutase (SOD) and peroxidase (PER) were analyzed. H2O2 exerted a biphasic effect. The inhibitory effect of H2O2 was related to the activation of the ERK and P38 pathway, NO production and apoptosis. The high proliferation was associated with a low level of H2O2 related to a low SOD and a high PER activities. Drugs capable of producing an increase in H2O2 levels could be used in cancer.
TL;DR: It is suggested that ZOL redirects DC differentiation toward a state of atypical maturation with allostimulatory function and this effect may go through prevention of Rap1A prenylation.
Abstract: Zoledronic acid (ZOL), an effective nitrogen-containing bisphosphonate against excessive bone loss, has been shown affecting the function of cells of both innate and acquired immunity. In this study, we tested the effect of ZOL on differentiation and maturation of human myeloid dendritic cells (DC). When ZOL (1.1 to 10 microM) was added to the culture of starting monocytes, but not to immature DC, the recovery rate of DC was markedly reduced in a concentration-dependent manner. The mature DC differentiated in the presence of ZOL had fewer and shorter cell projections. ZOL treatment affected DC differentiation and maturation in terms of lower expression of CD1a, CD11c, CD83, CD86, DC-SIGN, HLA-DR, and, in contrast, higher expression of CD80. IL-10 production by DC was inhibited by ZOL treatment whereas IL-12p70 secretion remained unchanged. Interestingly, ZOL augmented the allostimulatory activity of DC on naive CD4(++)CD45(+)RA(++) T cells in terms of their proliferation and interferon-gamma production. Addition of geranylgeraniol abrogated the effect of ZOL on DC differentiation and prenylation of Rap1A. It suggests that ZOL redirects DC differentiation toward a state of atypical maturation with allostimulatory function and this effect may go through prevention of Rap1A prenylation.
TL;DR: The results suggest that EEAA could suppress the cellular and humoral response in mice and provide evidence to understand the therapeutic effects of A. annua for treatment of some autoimmune diseases and an immunosuppressive natural products to further researches to be developed as Immunosuppressant.
Abstract: Artemisia annua has been widely used to treat autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis in traditional Chinese medicine In this study, the ethanol extract of A annua (EEAA) was evaluated for the immunosuppressive potentials on mice splenocyte proliferation in vitro, and the specific antibody and cellular immune responses in the ovalbumin (OVA)-immunized mice EEAA significantly suppressed concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro in a concentration-dependent manner EEAA also significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation in the OVA-immunized mice in a dose-dependent manner Meanwhile, the OVA-specific serum IgG, IgG1 and IgG2b antibody levels in the OVA-immunized mice were markedly reduced by EEAA The results suggest that EEAA could suppress the cellular and humoral response in mice This study provided evidence to understand the therapeutic effects of A annua for treatment of some autoimmune diseases and an immunosuppressive natural products to further researches to be developed as immunosuppressant
TL;DR: Results demonstrated that tigecycline alters cytokine production and reduces T-cell proliferation in vitro suggesting an immunomodulatory activity independent of its antimicrobial effect.
Abstract: The purpose of this study is to examine the in vitro modulatory effect of tigecycline on staphylococcal superantigen-induced T-cell activation and cytokines and chemokines production by human peripheral blood mononuclear cells (PBMC). Isolated human PBMC from ten healthy volunteers were stimulated by staphylococcal enterotoxin B (SEB) and Staphylococcal toxic shock syndrome toxin-1 (TSST-1) superantigens with varying concentrations of tigecycline. Cytokines IL-1β, IL-6, TNF-α, and chemokines MIP-1α and MIP-1β concentrations were measured along with T cell proliferation. Results demonstrated that tigecycline alters cytokine production and reduces T-cell proliferation in vitro suggesting an immunomodulatory activity independent of its antimicrobial effect.
TL;DR: Most of the proteins stable in SGF for more than 2 min showed similarity with characterized allergens on the basis of their molecular weights as in case of soybean, peanut, chickpea and black gram.
Abstract: Leguminous crops are the main source of protein in Asian subcontinent including India and their proteins may induce allergic reactions in sensitized individuals. Pepsin resistance of proteins is a characteristic feature of most of the allergens. Simulated gastric fluid (SGF) assay as validated by digestion of purified known allergenic and non-allergenic proteins was the basis of this study. Purified allergenic proteins were stable to SGF digestion contrary to rapidly digested non-allergenic proteins. Crude proteins extracts (CPE) of soybean, peanut, chickpea, black gram, kidney bean and Bengal gram were digested in vitro to detect their non-digestible proteins. Six proteins from soybean and seven from peanut remained undigested after SGF digestion. Likewise, seven proteins from chickpea (70, 64, 55, 45, 35, 20 and 18 kDa), ten from black gram (47, 30, 29, 28, 26, 24, 22, 16, 14 and 12 kDa), five from kidney bean (45, 29, 24, 20 and 6.5 kDa) and one from Bengal gram (20 kDa) remained undigested in SGF. Most of the proteins stable in SGF for more than 2 min showed similarity with characterized allergens on the basis of their molecular weights as in case of soybean, peanut, chickpea and black gram. Also, soybean and chickpea stable proteins showed IgE binding property with respective allergic patient's sera. The non-digestible proteins from the chickpea, black gram, kidney bean and Bengal gram are being reported for the first time by our group. IgE binding of SGF resistant soybean and chickpea proteins is being reported first time as well.