Showing papers in "Immunopharmacology and Immunotoxicology in 2018"
TL;DR: This review article focuses on animal models of arthritis induced in various species along with the genetic models and discussed the similarity and dissimilarities with respect to human RA.
Abstract: Rheumatoid Arthritis (RA) is an autoimmune systemic disorder of unknown etiology and is characterized by chronic inflammation and synovial infiltration of immune cells. RA is associated with decreased life expectancy and quality of life. The research on RA is greatly simplified by animal models that help us to investigate the complex system involving inflammation, immunological tolerance and autoimmunity. The animal models of RA with a proven track record of predictability for efficacy in humans include: collagen type II induced arthritis in rats as well as mice, adjuvant induced arthritis in rats and antigen induced arthritis in several species. The development of novel treatments for RA requires the interplay between clinical observations and studies in animal models. However, each model features a different mechanism driving the disease expression; the benefits of each should be evaluated carefully in making the appropriate choice for the scientific problem to be investigated. In this review article, we focus on animal models of arthritis induced in various species along with the genetic models. The review also discussed the similarity and dissimilarities with respect to human RA.
146 citations
TL;DR: Curcumin can be used as a potential and safe drug in the management of patients with remission and mild-to-moderate UC and its unrivaled safety profile indicate that it remains effective for the treatment of UC.
Abstract: Ulcerative colitis (UC) is a chronic, relapsing, remitting, and inflammatory disorder that afflicts millions of people around the world. It carries a substantial economic burden, reducing the quality of life, ability to work, and increasing disability. Conventional medical treatment of UC includes the use of aminosalicylates, corticosteroids, and immunosuppressive drugs. However, these medicines are not always effective due to some serious side effects. Nuclear factor-kappa B (NF-κB) is a key factor in the inflammatory setting and strongly affects the course of mucosal inflammation in UC. This review aims to describe the complex role of NF-κB in UC and discuss existing pharmacological attempts by curcumin for blocking NF-κB activation to develop new therapeutic strategies in UC. Several studies have shown intriguing pharmacologic effects associated with curcumin, which inhibits NF-κB expression by regulating NF-κB/IkB pathway and down-regulation expression of pro-inflammatory cytokines, such as Interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α. The efficacy of curcumin has been confirmed in several experimental models of UC. Furthermore, curcumin significantly induced clinical remission in active mild-to-moderate UC patients and reduced clinical relapse in quiescent UC patients. The inhibitory effects of curcumin on NF-κB and its unrivaled safety profile indicate that it remains effective for the treatment of UC. In addition, curcumin is a nontoxic, inexpensive, and easily available natural polyphenol. In conclusion, curcumin can be used as a potential and safe drug in the management of patients with remission and mild-to-moderate UC.
53 citations
TL;DR: TCA elicits the anti-inflammatory effects on LPS-stimulated macrophage activation via suppression of MAPKs phosphorylation, and pro-inflammatory gene expression, which provides important information regarding the use of TCA as a candidate therapeutic agent against inflammation.
Abstract: OBJECTIVES Inflammation is a primary response of the innate immune system against various infections. Macrophages are a type of immune cell that have a critical role in the inflammation. Recent studies reported that various natural compounds could regulate immune responses such as inflammation. Trans-cinnamaldehyde (TCA) is a natural compound from cinnamon, especially abundant in cinnamon bark. Previous studies reported that TCA has anti-biofilm, anti-microbial, and anti-cancer activities. However, the anti-inflammatory effects and the mechanism of TCA on macrophages are still unknown. MATERIALS AND METHODS Raw 264.7 murine macrophage cells were used in this study. Major assays were MTT, Griess assay, Western blot, enzyme-linked immunosorbent assay (ELISA) and reverse transcription (RT)-PCR analysis. RESULTS In this study, we investigated the anti-inflammatory effects of TCA on the RAW 264.7 murine macrophage cell line. TCA significantly decreased lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a dose-dependent manner. Moreover, TCA treatment significantly reduced mRNA expression and protein expression of inducible NO synthase (iNOS) in LPS-stimulated macrophages in a dose-dependent manner. TCA treatment also diminished the mRNA expression level and secretion of IL-1β, IL-6 and TNF-α in LPS-activated macrophages. TCA elicited the anti-inflammatory effects by inhibiting ERK, JNK and p38 MPAKs phosphorylation in the cells. DISCUSSION AND CONCLUSION TCA elicits the anti-inflammatory effects on LPS-stimulated macrophage activation via suppression of MAPKs phosphorylation, and pro-inflammatory gene expression. Therefore, this study provides important information regarding the use of TCA as a candidate therapeutic agent against inflammation.
44 citations
TL;DR: Downregulation of miR-340 inhibited GC cell proliferation, arrested cell cycle, and facilitated apoptosis through upregulating SOCS3 expression to suppress JAK-STAT3 signaling pathway.
Abstract: Objective: Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is closely related to tumorigenesis. Suppressors of cytokine signaling 3 (SOCS3) is a negativ...
41 citations
TL;DR: Rheumatoid arthritis pathogenesis and the potential application of new developments in CRISPR-mediated Treg genome editing in personalized therapy of RA are discussed.
Abstract: Introduction: Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biolo...
39 citations
TL;DR: In vitro experiments have shown induction of apoptosis by Amygdalin as a result of increased expression of Bax protein and caspase-3 and reduced expression of antiapoptotic BcL-2protein, and amygdalin inhibits NF-kβ and NLRP3 signaling pathways, and consequently has anti-inflammatory effect.
Abstract: Amygdalin, named as 'laetrile' and 'vitamin B-17' was initially supposed to be a safe drug for cancer treatment and was recognized by followers of natural medicine since it has been considered to be hydrolyzed only in cancer cells releasing toxic hydrogen cyanide (HCN), and thus destroying them. Unfortunately, current studies have shown that HCN is also released in normal cells, therefore it may not be safe for human organism. However, there have still been research works conducted on anti-cancer properties of this compound. In vitro experiments have shown induction of apoptosis by amygdalin as a result of increased expression of Bax protein and caspase-3 and reduced expression of antiapoptotic BcL-2protein. Amygdalin has also been shown to inhibit the adhesion of breast cancer cells, lung cancer cells and bladder cancer cells by decreased expression of integrin's, reduction of catenin levels and inhibition of the Akt-mTOR pathway, which may consequently lead to inhibition of metastases of cancer cells. It has also been revealed that amygdalin in renal cancer cells increased expression of p19 protein resulting in inhibition of cell transfer from G1-phase to S-phase, and thus inhibited cell proliferation. Other studies have indicated that amygdalin inhibits NF-kβ and NLRP3 signaling pathways, and consequently has anti-inflammatory effect due to reducing the expression of proinflammatory cytokines such as pro-IL-1β. Moreover, the effect of amygdalin on TGFβ/CTGF pathway, anti-fibrous activity and expression of follistatin resulting in activation of muscle cells growth has been reported. This compound might be applicable in the treatment of various cancer cell types.
37 citations
TL;DR: Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen and returned back renal oxidative stress-related parameters including glutathione, malondialdehyde, and activity of catalase and superoxide dismutase.
Abstract: Context: Acute kidney injury (AKI) is considered a major public health concern in today’s world. Sepsis‐induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major ou...
33 citations
TL;DR: It is demonstrated that ICT improves myelosuppression by improving bone marrow hematopoietic microenvironment, promoting the proliferation and differentiation of HSCs, inhibiting the apoptosis of H SCs and stimulating the expression of G-CSF and TPO.
Abstract: Context: Icaritin (ICT), an intestinal metabolite of prenylflavonoids from Herba Epimedii, has been known to regulate many immune processes. But there are little studies of ICT on hematopoietic fun...
33 citations
TL;DR: The hallmark immunobiology of Crohn’s disease and ulcerative colitis is described as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD.
Abstract: Inflammatory bowel diseases (IBDs) may result from dysregulated mucosal immune responses directed toward the resident intestinal microbiota. This review describes the hallmark immunobiology of Crohn's disease and ulcerative colitis as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD. Conventional therapies include 5-aminosalicylic acid, glucocorticosteroids, thiopurines, and methotrexate. Since 1997, monoclonal antibodies have gained widespread use. These consist of antibodies directed against pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12, and IL-23, or anti-homing antibodies directed against α4β7 integrin. Emerging oral therapies include modulators of intracellular signal transduction such as Janus kinase inhibitors. Vitamin D may help to regulate innate and adaptive immune responses. Modulation of the intestinal microbiota, using live microorganisms (probiotics), substrates for the colonic microbiota (prebiotics), or fecal microbiota transplantation (FMT), is in development. Dietary supplements are in widespread use, but providing evidence for their benefit is challenging. Stem cell treatment and nervous stimulation are promising future treatments.
30 citations
TL;DR: The role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function is summarized in this article and it is concluded that G PCR signaling is critical in regulating T cell immunity.
Abstract: AIM The aim of this paper is to clarify the critical role of GPCR signaling in T cell immunity. METHODS The G protein-coupled receptors (GPCRs) are the most common targets in current pharmaceutical industry, and represent the largest and most versatile family of cell surface communicating molecules. GPCRs can be activated by a diverse array of ligands including neurotransmitters, chemokines as well as sensory stimuli. Therefore, GPCRs are involved in many key cellular and physiological processes, such as sense of light, taste and smell, neurotransmission, metabolism, endocrine and exocrine secretion. In recent years, GPCRs have been found to play an important role in immune system. T cell is an important type of immune cell, which plays a central role in cell-mediated immunity. A variety of GPCRs and their signaling mediators (RGS proteins, GRKs and β-arrestin) have been found to express in T cells and involved T cell-mediated immunity. We will summarize the role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function in this article. RESULTS GPCR signaling plays an important role in T cell activation, homeostasis and function. CONCLUSION GPCR signaling is critical in regulating T cell immunity.
28 citations
TL;DR: The results indicate that B-ALL patients harbor high numbers of both MDSCs and Tregs cells, which opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-all patients at different treatment stages.
Abstract: Introduction: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechani...
TL;DR: A possible association between MDSC subsets and CCR5 is elucidated to provide a new potential target to enhance the efficacy of immunotherapy in patients with gastric cancer.
Abstract: Purpose: Myeloid derived suppressor cells (MDSC) play an important role in tumor immune evasion and its level significantly increased in patients with gastric cancer. Studies confirmed the associat...
TL;DR: Saccharomyces boulardii is, however, a plausible treatment option in the future, but more placebo-controlled clinical studies on both patients with ulcerative colitis and Crohn’s disease are needed.
Abstract: Context: Review of the yeast Saccharomyces boulardii as a treatment option for the inflammatory bowel diseases (IBD) ulcerative colitis and Crohn’s disease.Objective: IBD is caused by an inappropri...
TL;DR: This study was able to transformCD4 + T cells into CD4Foxp3+T cell by using stimulus like antibodies and cytokines and phosphorylated Ezh2 in the induced Treg cells using sodium butyrate to explore the relationship between Foxp3+ T cells induction and epigenetic modification.
Abstract: Context: CD4 + CD25+ regulatory T (Treg) lymphocytes are critical for immune homeostasis. Foxp3 (Forkhead Box protein P3) is always considered as a marker of function and identities determination o...
TL;DR: It is demonstrated that curcumin can inhibit the expression and production of inflammatory cytokines in M1 macrophages from BD patients compared with healthy controls.
Abstract: Objective: Behcet's disease (BD) is an auto-inflammatory disorder. Curcumin as a bio-active agent has anti-inflammatory properties. Effects of curcumin on the pathogenesis of BD are still not clear...
TL;DR: Artesunate has several mechanisms for augmenting the antitumor immune responses mediated by γδ T cells, which are suggested to be an efficacious agent in the treatment of hepatocellular carcinoma.
Abstract: Objective: To explore the effect and mechanism of artesunate on γδ T cell-mediated antitumor immune responses against hepatoma carcinoma cells (HepG2) in vitro.Methods: Human γδ T cells or HepG2 we...
TL;DR: Evidence is provided that 2′,4-dihydroxy-3′, 4′,6′-trimethoxychalcone possesses anti-inflammatory activity via targeting proinflammatory macrophages, and this anti- inflammatory chalcone is a promising compound for reducing inflammation.
Abstract: Context: Immune dysregulation has been implicated in the pathogenesis of many diseases. Macrophages play a crucial role contributing to the onset, progression, and resolution of inflammation. Macrophage inflammatory mediators are of considerable interest as potential targets to treat inflammatory diseases.Objective: The present study was conducted to elucidate the anti-inflammatory mechanism of 2′,4-dihydroxy-3′,4′,6′-trimethoxychalcone (1), the major chalcone isolated from Chromolaena odorata (L.) R.M.King & H.Rob, against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages.Materials and methods: Cell viability, nitric oxide (NO), and proinflammatory cytokines of LPS-activated RAW 264.7 cells were measured by MTT, Griess, and ELISA assays, respectively. Cell lysates were subjected to Western blotting for investigation of protein expression.Results and discussion: Treatment with the major chalcone 1 significantly attenuated the production of NO and proinflammatory cytokines, tum...
TL;DR: Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines, which is defined as a chronic inflammatory disease of the lung.
Abstract: Objective Allergic asthma is the most common type in asthma, which is defined as a chronic inflammatory disease of the lung. In this study, we investigated whether embelin (Emb), the major component of Ardisia japonica BL. (AJB), exhibits anti-inflammatory effects on allergic asthma via inhibition of NF-κB activity using A549 cells and asthmatic airway epithelial tissues. Methods Inflammation was induced in A549 cells, a human airway epithelial cell line, by IL-1β (10 ng/ml) treatment for 4 h. The effects of Emb on NF-κB activity and COX-2 protein expression in inflamed airway epithelial cells and human asthmatic airway epithelial tissues were analyzed via western blot. The secretion levels of NF-κB-mediated cytokines/chemokines, including IL-4, 6, 9, 13, TNF-α and eotaxin, were measured by a multiplex assay. Results Emb significantly blocked NF-κB activity in IL-1β-treated A549 cells and human asthmatic airway epithelial tissues. COX-2 expression was also reduced in both IL-1β-treated A549 cells and asthmatic tissues Emb application. Emb significantly reduced the secretion of IL-4, IL-6 and eotaxin in human asthmatic airway epithelial tissues by inhibiting activity of NF-κB. Conclusions The results of this study suggest that Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines.
TL;DR: It is suggested that targeting intra-tumor DCs to elicit expression of CD40 and ICOSL and present broad range of tumor antigens could yield effective anti-Tumor responses.
Abstract: Objective: To improve dendritic cells (DCs) function, we targeted DCs to over express CD40 and inducible costimulator ligand (ICOSL) costimulatory molecules along with total messenger RNA (mRNA) of tumor cells to achieve a safe and effective system for treatment of tumor. Materials and methods: We generated CD40 and ICOSL mRNA in vitro and manipulated DCs using chitosan nanoparticles and also lipofectamine transfection system then examined in vitro and in vivo. Results: Mice bone marrow derived DCs pulsed with total tumor mRNA/CD40 mRNA or ICOSL mRNA showed higher expression of DCs maturation markers (CD40, ICOSL, CD86, and MHC-II) and accelerated secretion of pro-inflammatory cytokines. Co-culture of DCs with T cells enhanced proliferation of T cells and shift toward stronger Th1 cytokine responses especially in presence of CD40 over expressed DCs. Intra-tumor administration of manipulated DCs to 4T1 tumor mice model showed delay in growth of tumor volume, trend to increase in mice survival, and stronger anti-tumor cytokines production in splenocytes of mice model (with higher efficacy of mRNA/chitosan nanoparticle system). Conclusions: Hence, we suggest that targeting intra-tumor DCs to elicit expression of CD40 and ICOSL and present broad range of tumor antigens could yield effective anti-tumor responses. In this regard, CD40 molecule manipulation trigger stronger functions, while mRNA/chitosan nanoparticles system could provide a high potent tool for targeting strategies.
TL;DR: In conclusion, the GA treatment can protect the brain tissue against EAE in mice with its antioxidant and anti-inflammatory properties.
Abstract: Aim: The aim of this study was to investigate the beneficial effects of 18β-glycyrrhetinic acid (GA) on the experimental allergic encephalomyelitis (EAE) in C57BL/6 mice. GA is a natural substance ...
TL;DR: The findings provide the possible mechanism of the anti-neuroinflammatory properties of Petatewalide B that result from beneficial responses in the AMPK/Nrf2-signaling pathway.
Abstract: OBJECTIVES Abnormal microglia secrete neuroinflammatory factors that play a pivotal role in neurodegenerative-disorder development. Thus, regulating abnormal microglia-activation could be a promising therapeutic strategy. The purposes of this study included investigating the effect of Petatewalide B on lipopolysaccharide- (LPS-) stimulated microglia and exploring the role of the AMPK/Nrf2- (adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2) signaling pathway in the anti-neuroinflammatory function of Petatewalide B. METHODS We divided the microglia into four groups: a control group, a Petatewalide B-treated group, an LPS-treated group, and an LPS and Petatewalide B-treated group. The four groups of microglia were experimented with, using the NO, ELISA, and promoter assays, and western blotting was conducted to determine LPS-stimulated neuroinflammatory responses. RESULTS We found that pretreatment with Petatewalide B strongly alleviates interleukin- (IL-) 1β, IL-6, and tumor-necrosis-factor-α (TNF-α) production, and suppresses iNOS and nitric oxide (NO) overexpression in LPS-stimulated microglia. The AMPK/Nrf2-signaling pathway is important for inducing anti-neuroinflammatory responses. Mechanistic studies report that Petatewalide B increases nuclear-Nrf2 translocation, and heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) expression in a dose-dependent manner. Furthermore, Petatewalide B significantly up-regulates HO-1 and NQO1 by specifically improving antioxidant-response-elements-transcription activity. We then investigated whether Nrf2/HO-1/NQO1 contribute to the anti-neuroinflammatory properties of Petatewalide B. Nrf2, HO-1, and NQO1 small-integrating-ribonucleic-acids (siRNAs) significantly blocked Petatewalide B-attenuated iNOS-promoter-activity in LPS-stimulated microglia. Furthermore, Petatewalide B also up-regulated AMPK-phosphorylation in a dose-dependent manner. We next evaluated whether blocking AMPK-phosphorylation using an inhibitor (compound C) would critically affect anti-neuroinflammatory responses. We found that the AMPK-phosphorylation is associated with nuclear-Nrf2 translocation and elevated HO-1 and NQO1 expression levels. Our data also showed that AMPK-inhibitor pretreatment significantly reverses Petatewalide B-attenuated iNOS-promoter-activity in LPS-stimulated microglia. CONCLUSIONS Our findings provide the possible mechanism of the anti-neuroinflammatory properties of Petatewalide B that result from beneficial responses in the AMPK/Nrf2-signaling pathway.
TL;DR: These data demonstrated the potential of Nanobody for application in targeting DLL4 and may provide a basis for the development of novel therapeutic techniques to inhibit growth and neovascularization of tumors.
Abstract: Objectives Angiogenesis targeting is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular development and its inhibitors have recently entered clinical trials for solid tumors. The aim of this study was to evaluate the possibilities of using anti-DLL4 antibody fragment as an angiogenesis maturation inhibitor. Materials and methods In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and assessed by western blotting and internalization assays. Functional assessments included MTT, apoptosis, and chicken chorioallantoic membrane (CAM) assays. Results Based on the results, 3Nb3 specifically binds to DLL4 and internalizes into MKN cell. Furthermore, 3Nb3 significantly inhibited the proliferation of cells and also neovascularization in the CAM. Conclusions These data demonstrated the potential of Nanobody for application in targeting DLL4. Our findings may provide a basis for the development of novel therapeutic techniques to inhibit growth and neovascularization of tumors.
TL;DR: This study indicated that AS PBMCs were hyper-responsive to MDP stimulation, implying an important role of NOD2 in the pathogenesis of inflammatory diseases including AS.
Abstract: Background: Ankylosing spondylitis (AS) is a common debilitating rheumatic disease in which the innate immune components especially the Interleukin (IL)-23/IL-17 axis related genes play important role in its pathogenesis. Nucleotide binding oligomerization domain-containing protein (NOD)2, as an innate receptor, is critical for IL-23 production in cells. Therefore, we aimed to stimulate NOD2 signaling and study its effects on cytokine production in peripheral blood mononuclear cells (PBMC) of these patients. Methods: PBMCs from 18 patients with active AS and 18 healthy individuals were separated by Ficoll-Hypaque density gradient centrifugation and cultured in the presence of muramyl dipeptide (MDP), as NOD2 ligand. Quantitative expression analysis of NOD1, NOD2, RIPK2, SLC15A4, NLRP1, NLRP3, IL23A, IL17A, IL1B, and TNFA genes was performed using Real-time polymerase chain reaction (PCR). Finally, protein changes of IL23A and IL17A expression were validated using enzyme linked immunosorbent assay (ELISA). Results: Apart from NOD1 that tend to be downregulated in the controls, all the selected genes showed overexpression in response to MDP in cells from the studied groups. Except RIPK2, all the genes had higher expression changes upon MDP stimulation in the AS population. Overexpression of IL23A and IL17A were confirmed at protein levels using ELISA. The strong positive correlation between NLRP3 and NOD2 was decreased after stimulation but new correlations between NLRP3 and IL1B, RIPK2 and SLC15A4 were observed after treatment. Conclusions: This study indicated that AS PBMCs were hyper-responsive to MDP stimulation. This observation implies an important role of NOD2 in the pathogenesis of inflammatory diseases including AS.
TL;DR: In the present investigation, hecogenin and its combination prevent destruction of cartilage and protect synovial membrane with improving health status through haematonic properties and down regulation of various cytokines.
Abstract: Hecogenin is a steroidal sapogenin isolated from the leaves of Agave genus species that plays an important role in the treatment of a variety of inflammatory diseases. The aim of the present study ...
TL;DR: AZ as an AQP1 inhibitor has a powerful therapeutic effect on rat AIA via inhibiting NF-κB activation, suggesting AQP 1 inhibition might be of potential clinical interest in RA treatment.
Abstract: Objectives: Previous studies have shown that aquaporin 1 (AQP1) is up-regulated in synovium and cartilage of rheumatoid arthritis (RA) patients and that AQP1 may be involved in joint swelling and s...
TL;DR: Results indicated that AS and its active compound, DEQA may improve mast cell-mediated inflammatory diseases.
Abstract: Objectives: Artemisia scoparia Waldst. et Kit. (AS) has been used to treat inflammation, urticaria and hepatitis. However, the scientific studies of AS and its active compound for inflammatory reac...
TL;DR: Valsartan showed a significant protective effect against bleomycin-induced PF, which was at least partly due to antifibrotic/profib rotic cytokine regulation and reduced NF-κB expression.
Abstract: Objective: Pulmonary fibrosis (PF) is a chronic respiratory system disease. The role of inflammation and angiotensin in the development and progression of PF has previously been demonstrated. Alter...
TL;DR: The results indicated that the protective effects of MgIG on D-GaIN/LPS-induced acute liver injury might be correlated with its capacity to regulate the p38-MAPK and NF-κB signaling pathways.
Abstract: CONTEXT Acute hepatic failure involves in serious inflammatory responses and leads to a high mortality. Magnesium isoglycyrrhizinate (MgIG), a magnesium salt of 18-α glycyrrhizic acid (GA) stereoisomer, has been shown anti-inflammatory activity previously. OBJECTIVE This study aimed to investigate the protective effects of MgIG, a hepatocyte protective agent, on D-galactosamine and lipopolysaccharide (D-GaIN/LPS)-induced acute liver injury in rats, and meanwhile explore the molecular mechanism. MATERIALS AND METHODS Male Sprague-Dawley (SD) rats were injected with D-GaIN/LPS (800 mg/kgBW/10 μg/kgBW) with or without administration of MgIG (225 mg/kg once 6 h after D-GaIN/LPS injection and MgIG 45 mg/kg twice in another 12 h, intraperitoneal injection). Rats were sacrificed 24 h after D-GaIN/LPS injection, the blood and liver samples were collected for future inflammation and hepatotoxicity analyses. RESULTS MgIG significantly inhibited D-GaIN/LPS-induced inflammatory cytokines production and hepatotoxicity as indicated by both diagnostic indicators of liver damage [aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels] and histopathological analysis. Western blot analysis demonstrated that MgIG significantly decreased p38-mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation induced by D-GaIN/LPS. CONCLUSION The results indicated that the protective effects of MgIG on D-GaIN/LPS-induced acute liver injury might be correlated with its capacity to regulate the p38-MAPK and NF-κB signaling pathways.
TL;DR: In this article, the authors explored the mechanisms of cytotoxicity of CoNPs and Co2+ and developed strategies to reduce this toxicity with α-tocopherol treatment.
Abstract: Context Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co2+) are the most serious adverse effect in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it. Objective We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co2+ and developed strategies to reduce this cytotoxicity with α-tocopherol treatment. Methods To evaluate the protective effect of α-tocopherol, Balb/3T3 cells were pretreated with 10 μM α-tocopherol for 24 h. The cells were then exposed to different concentrations of CoNPs and Co2+ for 12 h, 24 h and 48 h. The cell viabilities, reactive oxygen species (ROS), inflammatory cytokines and MAP kinase (MAPK) levels were measured. Results CoNPs and Co2+ can induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, α-tocopherol pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co2+, decrease ROS production and decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK pathway may be involved in the protection of α-tocopherol against cytotoxicity induced by CoNPs and Co2+ in vitro. Conclusions Our results provide new insights into the potential therapeutic use of α-tocopherol in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries.
TL;DR: Due to reducing mRNA expression and concentrations of TNFα and IL6, celastrol can serve as a suitable choice to control cytokine-induced inflammation in IAV infection, and therefore it can be used with current antiviral drugs.
Abstract: Context: The influenza A virus (IAV) causes severe respiratory disease that remains a leading reason for morbidity and mortality. Previous studies have indicated that influenza complications in add...