Showing papers in "Inflammation Research in 2013"
TL;DR: This review concisely summarizes the role of this pro-inflammatory cytokine during inflammation, focused mainly on TNF-α intracellular signaling and its influence on the typical inflammatory features in the organism.
Abstract: Introduction
Inflammation is a very important part of innate immunity and is regulated in many steps. One such regulating step is the cytokine network, where tumor necrosis factor α (TNF-α) plays one of the most important roles.
502 citations
TL;DR: It appears that most components of the immune system are potentially endowed with dual functions i.e., promoting tumor development on the one hand and restraining tumorDevelopment on the other and hence immune system can be considered as a double-edged sword in cancer.
Abstract: Objective
The objective of the review is to examine the role of innate and adaptive immune cells in cancer
142 citations
TL;DR: The impaired apoptosis in RA synovium might result from increased autophagy, which in turn could be due to the deregulation of miRNA-30a.
Abstract: Defective apoptosis contributes to the massive synovial hyperplasia in rheumatoid arthritis (RA), but the mechanism is largely unknown. To investigate the reasons for the reduced apoptosis in RA synovium, we analyzed autophagy and its relationship to apoptosis in synovial tissues from RA and osteoarthritis (OA) patients. Synovial tissues were obtained from seven RA and 12 OA patients undergoing knee replacement surgery. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and staining for p85 fragment of PolyADP-ribose polymerase (PARP). Autophagy was determined by immunoblotting for the autophagic markers Beclin-1 and LC3. MicroRNA-30a (miR-30a), which targets Beclin-1, was measured by real-time RT-PCR. The interplay between autophagy and apoptosis was determined via Spearman’s correlation analysis. In comparison with OA, the synovial tissues from RA displayed decreased TUNEL-positive nuclei (P < 0.01). In contrast, Beclin-1 and LC3 were overexpressed in the synovial lining layers of RA, which was correlated with decreased levels of miR-30a. Moreover, there was a significant reverse relationship between apoptosis and autophagy in RA synovial tissues (P < 0.01 and r = −0.8937). The impaired apoptosis in RA synovium might result from increased autophagy, which in turn could be due to the deregulation of miRNA-30a.
115 citations
TL;DR: This study demonstrates that salidroside is an effective suppressor of inflammation and may be a candidate for the prophylaxis of mastitis.
Abstract: Background and objective
Mastitis is defined as inflammation of the mammary gland in domestic dairy animals and humans. Salidroside, a major component isolated from Rhodiola rosea L., has potent anti-inflammatory properties, but whether it can be used in mastitis treatment has not yet been investigated. The aim of this study was to assess the protective effects of salidroside against lipopolysaccharide (LPS)-induced mastitis in mice and the mechanism of action.
102 citations
TL;DR: IL-1β induces a reversible contractile dysfunction associated with impaired response to β-receptor stimulation, and left ventricular fractional shortening reduced at 4 h versus vehicle and was maintained throughout chronic dosing.
Abstract: Inflammatory mediators play a key role in the development and progression of heart failure. Interleukin-1β (IL-1β) is a prototypical inflammatory cytokine that suppresses myocyte contractility following acute administration. Healthy mice were randomly assigned to daily intraperitoneal injections of recombinant murine IL-1β (3 μg/kg in 0.2 ml) or matching volumes of NaCl 0.9 % solution (vehicle) for 15 days. Echocardiography was performed at baseline and 4 h (acute), followed by repeat measurements immediately prior to IL-1β or saline injections on days 5, 10, and 15 (chronic). Final echocardiography was performed on day 20 (5 days after last treatment). A subgroup of animals underwent isoproterenol challenge to evaluate contractile reserve at baseline, 4 h (acute), 15 days (chronic) and 20 days (recovery). IL-1β reduced left ventricular fractional shortening (LVFS) at 4 h versus vehicle (−24 vs. 0 %, respectively, P < 0.05). This reduction was maintained throughout chronic dosing at day 15. IL-1β-treated mice also showed impaired contractile reserve with a right shift of the dose-response curve to isoproterenol (P < 0.05) at 4 h and 15 days. By day 20, 5 days after stopping IL-1β, LVFS and contractile reserve had returned to baseline. IL-1β induces a reversible contractile dysfunction associated with impaired response to β-receptor stimulation.
96 citations
TL;DR: Baicalein suppressed the nuclear translocation of STAT1 and STAT3 and inhibited production of iNOS upon LPS-stimulation, resulting in the inhibition of releases of NO and pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, in a dose-dependent manner.
Abstract: Objective
To investigate the precise molecular mechanisms by which baicalein exerts beneficial biochemical activities in RAW264.7 macrophages treated with LPS.
82 citations
TL;DR: These results demonstrate that ROS regulates not only the priming stage, but also the activation stage, of NLRP3 inflammasome activation in LPS + ATP-activated macrophages.
Abstract: Reactive oxygen species (ROS) plays a critical role in the regulation of NLRP3 inflammasome activation. However, the ROS-mediated signaling pathways controlling NLRP3 inflammasome activation are not well defined. Using lipopolysaccharide (LPS) and adenosine triphosphate (ATP) activated murine macrophages as the testing model, cytokine release and protein expression were quantified by enzyme-linked immunosorbent assay and Western blot, respectively. ROS was scavenged by N-acetyl cysteine; NADPH oxidase, the major source of ROS, was inhibited by diphenyliodonium, apocynin or gp91-phox siRNA transfection; and protein kinase was inhibited by its specific inhibitor. LPS-induced NLRP3 protein expression was regulated through the NADPH oxidase/ROS/NF-κB-dependent, JAK2/PI3-kinase/AKT/NF-κB-dependent, and MAPK-dependent pathways, while ATP-induced caspase-1 activation was regulated through the NADPH oxidase/ROS-dependent pathway. These results demonstrate that ROS regulates not only the priming stage, but also the activation stage, of NLRP3 inflammasome activation in LPS + ATP-activated macrophages.
82 citations
TL;DR: The results indicate that CGA can efficiently inhibit LPS-induced proinflammatory responses in HSCs and the anti-inflammatory effect may be due to the inhibition of LPS/ROS/NF-κB signaling pathway.
Abstract: This study was aimed at investigating the effect of chlorogenic acid (CGA) on lipopolysaccharide (LPS)-induced proinflammatory signaling in hepatic stellate cells (HSCs). An immortalized rat HSC line was cultured in vitro and treated with LPS in the absence or presence of CGA. Reactive oxygen species (ROS) production in the HSCs was monitored by flow cytometer using DCFH-DA. The protein expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB), and p-IκB-α were determined by Western blot. The mRNA expression levels of TLR4, MyD88, monocyte chemotactic protein 1(MCP-1), and interleukin 6 (IL-6) were detected by RT-PCR. The levels of MCP-1 and IL-6 in the culture supernatant of HSCs were measured by ELISA. CGA had no effect on expression of TLR4 and MyD88. However, the treatment of CGA can inhibit LPS-induced production of ROS in HSCs. Meanwhile, CGA can inhibit LPS-induced nuclear translocation of NF-κB and IκB-α phosphorylation in HSCs, as well as NAC (a ROS scavenger). The mRNA expression and the levels of MCP-1 and IL-6 in the culture supernatant of the HSCs in this study were elevated by LPS stimulation and inhibited by CGA treatment, as well as NAC and PDTC (a NF-κB inhibitor). Our results indicate that CGA can efficiently inhibit LPS-induced proinflammatory responses in HSCs and the anti-inflammatory effect may be due to the inhibition of LPS/ROS/NF-κB signaling pathway.
76 citations
TL;DR: Results indicate that silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells, suggesting that silIBinin could be used for the treatment of mast cell-derived allergic inflammatory diseases.
Abstract: Background
Silibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum. It has been used for the treatment of hepatitis and inflammation-related diseases. In the present study, the effects of silibinin on allergic inflammation and its signaling were investigated in the induced human mast cells.
70 citations
TL;DR: The simultaneous secretion and release of multiple mediators such as proinflammatory cytokines and chemokines, cell adhesion molecules, and growth factors were found to be involved in the initiation of systemic inflammation in neonatal sepsis.
Abstract: Objective and design
Sepsis refers to severe systemic inflammation in response to invading pathogens. To understand the molecular events that initiate the systemic inflammatory response, various inflammatory mediators were analyzed in neonatal sepsis samples and compared with normal samples.
64 citations
TL;DR: Tregs are more radioresistant, less prone to radiation-induced apoptosis, and have faster repopulation kinetics than CD4+Foxp3− cells, but irradiated T Regs are functionally compromised, having a reduced suppressive capacity.
Abstract: Objective
Radiotherapy affects antitumor immune responses; therefore, it is important to study radiation effects on various compartments of the immune system. Here we report radiation effects on the homeostasis and function of regulatory T (Treg) cells, which are important in down-regulating antitumor immune responses.
TL;DR: Results support the anti-inflammatory properties of skimmianine and its multi-targeted mechanism of action, suggesting its potential therapeutic efficacy in various inflammatory diseases.
Abstract: The present study evaluates the anti-inflammatory effect of the quinoline alkaloid skimmianine (SKM), isolated from Ruta graveolens L., against carrageenan-induced acute inflammation. SKM at a dose of 5.0 mg/kg body weight was found to be the minimal concentration for maximal edema inhibition. Carrageenan suspension was administered into the sub-plantar tissue of the right hind paw 1 h after SKM and diclofenac (20 mg/kg) administration (i.p.). Paw edema was determined 3 h after carrageenan administration. The rats were then killed and mRNA expressions of TNF-α and IL-6, levels of PGE2 and TBARS, activities of COX-2, 5-LOX, SOD, catalase, glutathione peroxidase (GPx) and myeloperoxidase (MPO) and the level of nitrite were measured. SKM treatment resulted in a decrease in the mRNA levels of TNF-α and IL-6, which are upstream events of the inflammatory cascade. The levels of PGE2 and NO and the activities of COX-2 and 5-LOX were also significantly reduced after SKM treatment. Neutrophil infiltration, lipid peroxidation and associated oxidative stress in the paw tissue were reduced following SKM treatment. These results support the anti-inflammatory properties of skimmianine and its multi-targeted mechanism of action, suggesting its potential therapeutic efficacy in various inflammatory diseases.
TL;DR: The anti-inflammatory action of Pae in the murine model of ACD may be related to its regulation of an imbalanced cytokine production.
Abstract: Paeoniflorin (Pae) was previously reported to inhibit inflammation in the skin of mice with allergic contact dermatitis (ACD); however, the mechanism remains unclear. The primary purpose of this study was to investigate the effect of Pae on the regulation of cytokine production in a murine model of ACD. ACD was induced in the mice by repeated application of dinitrochlorobenzene (DNCB) to their skin. Cutaneous inflammation was evaluated by measuring ear swelling and by histological examination. The cytokine levels were measured by enzyme-linked immunosorbent assays. The results showed that topical application of DNCB caused obvious swelling and inflammatory cell infiltration. Treatment with Pae (70 or 140 mg/kg/d) significantly inhibited the cutaneous inflammation and decreased thymocyte proliferation in the mice with ACD. Additional data indicated that Pae increased interleukin-4 (IL-4) and IL-10 production but reduced IL-2 and IL-17 levels in the serum as well as in thymocyte and splenocyte culture supernatants. As expected, IL-2 and IL-17 levels in the serum displayed a significant positive correlation with the severity of skin inflammation. In contrast, IL-4 and IL-10 levels were negatively correlated with the inflammation. The anti-inflammatory action of Pae in the murine model of ACD may be related to its regulation of an imbalanced cytokine production.
TL;DR: This study indicates that NF-κB plays an important role in the process of TNF-α-induced apoptosis in AECs, via regulation of the expression of Bcl-2 and Bax.
Abstract: Objective
Apoptosis of alveolar epithelial cells (AECs) plays a key role in acute lung injury (ALI). Understanding the underlying mechanism is conducive to the treatment of ALI. The goal of this study was to determine the possible involvement of nuclear factor-κB (NF-κB)/p65 and Bax/Bcl-2 in tumor necrosis factor-α (TNF-α)-induced apoptosis in AECs.
TL;DR: In-vivo investigations showed that crocin ameliorated cartilage degeneration and that expression of the MMP-1, -3 and -13 genes in cartilage was significantly inhibited by crocin, suggesting that the anti-inflammatory activity of crocin may be of potential value in the prevention and treatment of osteoarthritis.
Abstract: Objective
Interleukin-1β-mediated production of matrix metalloproteinases (MMPs) plays a pivotal role in the process of osteoarthritis. Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been used in Chinese traditional medicine. In this study, we aimed to investigate the effects of crocin on MMP-1, MMP-3 and MMP-13 expression in rabbit chondrocytes induced by interleukin-1β (IL-1β) and in an experimental rabbit model induced by anterior cruciate ligament transection.
TL;DR: In this article, the authors tested the hypothesis that acute myocardial infarction (AMI) results in remote organ (renal) inflammation and adverse left ventricular remodelling and found that myocardium remote to the infarct zone also becomes inflamed.
Abstract: Rationale and Objective
Acute myocardial infarction (AMI) results in the recruitment of leukocytes to injured myocardium. Additionally, myocardium remote to the infarct zone also becomes inflamed and is associated with adverse left ventricular remodelling. Renal ischaemic syndromes have been associated with remote organ inflammation and impaired function. Here, we tested the hypothesis that AMI results in remote organ (renal) inflammation.
TL;DR: Flupirtine is the first therapeutically used KV7 channel activator with additional GABAAergic mechanisms and thus the first representative of a novel class of analgesics and its back-up compound, the bioisostere retigabine, has been approved for the treatment of epilepsy.
Abstract: Flupirtine was developed long before KV7 (KCNQ) channels were known. However, it was clear from the beginning that flupirtine is neither an opioid nor a nonsteroidal anti-inflammatory analgesic. Its unique muscle relaxing activity was discovered by serendipity. In the meantime, broad and intensive research has resulted in a partial clarification of its mode of action. Flupirtine is the first therapeutically used KV7 channel activator with additional GABAAergic mechanisms and thus the first representative of a novel class of analgesics. The presently accepted main mode of its action, potassium KV7 (KCNQ) channel activation, opens a series of further therapeutic possibilities. One of them has now been realized: its back-up compound, the bioisostere retigabine, has been approved for the treatment of epilepsy.
TL;DR: The association of circulatory Th17 and Treg lymphocytes with mortality in severe sepsis may be due to the change in total CD4+ T lymphocytes, and in survivors, Th17 differentiation and counts were restored.
Abstract: Objective and design
T helper 17 (Th17) and regulatory T (Treg) lymphocytes might play important roles in patients with severe sepsis. The association of Th17 or Treg lymphocytes with survival is also unclear.
TL;DR: This study proves the chemopreventive efficacy of hesperidin against the deleterious traits of colon carcinogenesis including accelerated proliferation, inflammation and persistent oxidative stress.
Abstract: Colon cancer is a common malignant neoplasm causing huge morbidity and mortality worldwide. Current therapeutic interventions are unsatisfying, which necessitates novel chemopreventive strategies. The present study was intended to elucidate the chemopreventive efficacy of hesperidin against azoxymethane (AOM)-induced mouse colon carcinogenesis. Swiss albino mice were subjected to intraperitoneal injections of AOM once a week for 3 consecutive weeks. Hesperidin treatments were provided in the initiation or post-initiation phases. The number and multiplicity of aberrant crypt foci (ACF), tumor incidence and antioxidant status were determined. Histopathological analyses, proliferating cell nuclear antigen (PCNA) index and modulations in the expression of inflammatory markers such as nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were studied. Hesperidin treatments significantly inhibited the number and multiplicities of AOM-induced ACF and tumor incidence. Hesperidin reduced oxidative stress parameters and enhanced antioxidant status. A marked decrease in the PCNA index was evident on hesperidin administration. Hesperidin treatments caused a prominent downregulation of NF-κB and its target molecules iNOS and COX-2, thereby combating inflammation. This study proves the chemopreventive efficacy of hesperidin against the deleterious traits of colon carcinogenesis including accelerated proliferation, inflammation and persistent oxidative stress.
TL;DR: Osteoarthritis is the most widespread chronic degenerative joint disorder, characterized by progressive destruction of articular cartilage, subchondral bone alterations, formation of osteophytes and synovitis, and many of them are evolutionarily conserved.
Abstract: Osteoarthritis (OA) is the most widespread chronic degenerative joint disorder, characterized by progressive destruction of articular cartilage, subchondral bone alterations, formation of osteophytes and synovitis. MicroRNAs (miRNAs) are a class of endogenous and non-coding single-strand RNAs with a length of about 22 nucleotides, and many of them are evolutionarily conserved. miRNAs have been implicated in the process of development and pathogenesis of diseases, and tissue-specific miRNA functional studies in mice have revealed both pathogenic and protective functions. miRNA-140 (miR-140) was shown to be specifically expressed in cartilage tissues in developing zebrafish and mouse embryos during the development of both long and flat bones. Recently, miR-140 has been reported in many studies to play significant roles in OA pathogenesis. Although the previous results were not always consistent, the molecular mechanisms of the regulation and dual function of miR-140 in cartilage homeostasis and development have been established in previous studies. Further elucidation of the molecular basis of miR-140 will uncover synergistic inhibitory effects of miR-140 and other factors on OA pathogenesis, and provide a novel means of treating OA disease.
TL;DR: Findings lend pharmacological support to the reported folkloric use of C. halicacabum in the treatment and management of painful, arthritic inflammatory conditions.
Abstract: The present work was carried out to investigate the free radical scavenging activity of the ethanol extract of C. halicacabum leaves (EECH), to study its antioxidant properties and anti-rheumatic effects in Wistar rats with CFA-induced arthritis, and to profile the phenolic components thereof by LC–MS/MS. The free radical scavenging activities of the extract was evaluated by NO and superoxide anion scavenging assays. Arthritis was induced to the albino Wistar rats by CFA. Fifteen days after CFA induction, arthritic rats received EECH orally at the doses of 250 and 500 mg/kg daily for 20 days. Diclofenac sodium was used as reference standard. EECH is subjected to LC–MS/MS analysis for the identification of phenolic compounds. The IC50 value of the EECH to scavenge the NO and superoxide radicals are 83 and 60 μg/ml respectively. Ultrasonography and histology images of hind limb in EECH treated groups confirmed the complete cartilage regeneration. The LC/MS/MS analysis indicated the presence of anti-inflammatory compounds luteolin-7-O-glucuronide, apigenin-7-O-glucuronide and chrysoeriol. These findings lend pharmacological support to the reported folkloric use of C. halicacabum in the treatment and management of painful, arthritic inflammatory conditions.
TL;DR: The data strongly suggest that PPs predominantly affect delayed molecular and cellular events initiated in NHEK by solar UV rather than primary photochemical reactions.
Abstract: The understanding of the anti-inflammatory mechanisms of action of plant polyphenols (PPs) and clarification of the relationship between their anti-inflammatory and antioxidant properties may result in a new therapeutic approach to skin cancers. To elucidate the underlying mechanism, we analyzed the ability of PPs to attenuate inflammatory, metabolic and oxidative cellular responses to UV irradiation. Normal human epidermal keratinocytes (NHEK) were exposed to physiologically relevant dose of solar-simulated UV irradiation. Effects of pre- and post-treatment with PPs on the overproduction of peroxides and inflammatory mediators (mRNA and protein) were analyzed using real-time RT-PCR, enzyme-linked immunosorbent and fluorometric techniques. Differences between the effectiveness of pre- and post-treatment with polyphenols was found. In particular, PPs post-treatment, but not pretreatment, completely abolished overexpression of Cyp1a1 and Cyp1b1 genes and elevation of intracellular peroxides in NHEK irradiated by UV. Post-treatment with PPs also more efficiently than pretreatment prevented UV-induced overexpression of IL-1 beta, IL-6 and COX2 mRNAs. Our data strongly suggest that PPs predominantly affect delayed molecular and cellular events initiated in NHEK by solar UV rather than primary photochemical reactions. PPs may be important component in cosmetic formulations for post-sun skin care.
TL;DR: Dexmedetomidine could reduce the mortality rate and inhibit pro-inflammatory cytokine responses during polymicrobial sepsis in mice.
Abstract: We investigated whether dexmedetomidine provided protective effects on cecal ligation and puncture (CLP)–induced septic mice, through suppressing the expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6)] and high mobility group box 1 (HMGB1). The model of sepsis was set up by CLP in 136 male BALB/c mice (40 mice for survival studies and 96 for cytokine studies) which were divided into four groups, including a C, CLP, DEX + CLP and CLP + DEX group. The serum levels of TNF-α, IL-6 and HMGB1 were detected at 6, 12, 24 and 48 h after operations, and lung HMGB1 mRNA were analyzed at 24 and 48 h. The mortality rates were calculated 7 days after the operations. The mortality rates 7 days after operations were significantly lower in the CLP + DEX (50 %) and DEX + CLP (30 %) groups than in the CLP group (90 %). Serum concentrations of IL-6 and TNF-α decreased significantly in dexmedetomidine administration groups compared with the CLP group. The levels of HMGB1 and lung HMGB1 mRNA were lower in the dexmedetomidine administration groups than in the CLP group. There was a significant correlation between lung HMGB1 mRNA and serum HMGB1(r = 0.858). Dexmedetomidine could reduce the mortality rate and inhibit pro-inflammatory cytokine responses during polymicrobial sepsis in mice.
TL;DR: It is clearly demonstrated that polyamines are involved in the anti-inflammatory effect by reducing dermal edema thickness and other inflammatory mediators like NO and cytokines in a dose-dependent manner.
Abstract: Natural polyamines are some of the most abundant polycationic molecules in eukaryotic cells, regulating gene expression. Polyamines have been reported to possess anti-inflammatory activities in many model inflammation systems. However, there is no report on their role in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermal edema. Mouse ear edema was induced by TPA. Edema biopsies were investigated using H&E staining. Levels of nitric oxide (NO) were determined using the Griess reaction. Tumor necrosis factor α (TNFα) and interleukin (IL)-1β levels in cell supernatants were measured by TNFα and IL-1β ELISA kits. Spermidine and spermine caused significant decreases in ear thickness, water content, and neutrophil infiltrations in comparison with negative control (p < 0.05). External polyamines reduced the levels of inflammatory mediators such as NO, TNFα, and IL-1β in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Spermine had a higher inhibitory effect on the production of cytokines such as IL-1β and TNFα in LPS-stimulated murine macrophages compared to other polyamines. Our findings clearly demonstrated that polyamines are involved in the anti-inflammatory effect by reducing dermal edema thickness and other inflammatory mediators like NO and cytokines in a dose-dependent manner.
TL;DR: It is demonstrated that CS1 plays an inhibitory role in human monocytes to control proinflammatory immune responses and cross-linking CS1 resulted in reduced production of proinflammatory cytokines TNF-α and IL-12p70 by LPS-activated monocytes.
Abstract: Objective and design
CS1 (CRACC, CD319, SLAMF7) is a member of the Signaling Lymphocyte Activation Molecule family expressed on immune cells mediating host defense. CS1 is a self-ligand and has both activating and inhibitory functions in Natural Killer cells. However, the function of CS1 in human monocytes is currently unknown. The objective of this study was to evaluate the control of CS1 surface expression in activated monocytes and to assess the effect of CS1 triggering on proinflammatory cytokine production by monocytes.
TL;DR: The IL17F (rs763780, 7488T/C) variant was associated with an increased risk for the development of CD, and affected some clinical features of UC and CD and there was a risk haplotype in IL17A which could increase the risk of UC.
Abstract: Objective
Interleukin-17A and interleukin-17F (IL-17A and IL-17F) are candidate genes for chronic inflammatory disease. We investigated the association between IL17A/F gene polymorphisms and susceptibility to and clinical features of inflammatory bowel disease (IBD).
TL;DR: Cucurbitacin E displayed anti-inflammatory effects through suppression of NF-κB nuclear translocation leading to a decreased expression of TNF-α and IL-1β in LPS-stimulated RAW 264.7 cells.
Abstract: Cucurbitacin E (CuE), a triterpenoid compound isolated from Cucurbitaceae plants, possesses a wide range of biological activities including anti-inflammatory properties. The present study aimed to investigate the anti-inflammatory effect of CuE and the underlying mechanism of action. The anti-inflammatory effect of CuE was evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Cell proliferation was assessed using a modified MTT assay. Cell cycle distribution was analyzed by propidium iodide staining. The actin cytoskeleton was examined by immunofluorescent staining. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β was determined by intracellular cytokine staining. G-actin level and nuclear factor (NF)-κB nuclear translocation were detected by immunoblotting. CuE inhibited cell proliferation and induced cell cycle arrest at G2/M phase in RAW 264.7 cells. CuE also suppressed LPS-induced cell spreading and pseudopodia formation. These effects were associated with decreased G-actin level and severe actin aggregation. Moreover, CuE significantly inhibited both TNF-α and IL-1β production in LPS-stimulated RAW 264.7 cells. This was likely mediated by suppressing LPS-induced nuclear translocation of NF-κB, a critical transcription factor responsible for pro-inflammatory cytokine expression. CuE displayed anti-inflammatory effects through suppression of NF-κB nuclear translocation leading to a decreased expression of TNF-α and IL-1β in LPS-stimulated RAW 264.7 cells.
TL;DR: The data clearly suggest that venom-induced oxidative stress and inflammation is also responsible for oxidative burst and cell death in the circulation, which may worsen even after anti-venin therapy.
Abstract: Background and objective
The snakebite mortality rate has been significantly reduced due to effective anti-venin therapy. The intravenously infused anti-venom will neutralize free and target-bound toxins but fails to neutralize venom-induced inflammation and oxidative stress, as the antigen–antibody complex itself is pro-inflammatory. Therefore, an auxiliary therapy is necessary to treat secondary/overlooked envenomation complications.
TL;DR: Alveolar macrophages can produce and release IL-22 during the activation of the innate immune response and thereby constitute a potentially important regulator of mucosal host defence in the lungs.
Abstract: Interleukin (IL)-22 is important for mucosal host defense. Whereas previous studies focus on lymphocytes as sources of IL-22, we determined whether IL-22 is produced by inflammatory cells in the lungs other than T-lymphocytes during the activation of the innate immune response. Inflammatory cells in the lungs of Balb/c mice were primed by endotoxin (LPS, 10 μg) or peptidoglycan (PG, 40 μg) intranasally (3 days). After CD3 + cell depletion, lung homogenates were re-stimulated 24 h with LPS (100 ng/ml), PG (10 μg/ml), IL-23 (100 ng/ml) or vehicle. Human BAL macrophages were stimulated 24 h with PG (50 μg/ml) and IL-23 (100 ng/ml) or vehicle. The release of IL-22 was measured with ELISA and intracellular IL-22 with immunostaining. For statistics, either Dunnett or Students t test method was employed (n = 3–8). Re-stimulation in vitro increased concentrations of mouse IL-22 protein irrespective of priming in vivo. A majority of macrophages in mouse lung and BAL samples displayed immunostaining for IL-22. In analogy, human BAL macrophages released IL-22 protein, and a third of these cells displayed immunostaining for IL-22. Alveolar macrophages can produce and release IL-22 during the activation of the innate immune response and thereby constitute a potentially important regulator of mucosal host defence in the lungs.
TL;DR: The potential anti-inflammatory effect of p-Coumaric acid against monosodium urate crystal-induced inflammation in rats is revealed, as evidenced by the histopathology of the ankle joints.
Abstract: This study was conducted to evaluate the effect of p-Coumaric acid, a common dietary phenol, on monosodium urate crystal-induced inflammation in rats—an experimental model for acute gouty arthritis. Paw edema, levels/activities of lysosomal enzymes, lipid peroxidation, enzymic antioxidants and a histopathological examination of ankle joints were evaluated in control and monosodium urate crystal-induced inflamed rats. Further, an acetic acid-induced writhing test and tail immersion test were employed to screen for analgesic effects, yeast-induced pyrexia was used to test for antipyretic effects, and gastric ulceration was used to evaluate ulcerogenic effects. A significant increase in paw edema, lysosomal enzyme activity and lipid peroxidation levels was observed in monosodium urate crystal-induced rats, whereas activities of enzymic antioxidants were found to be decreased when compared to control rats. Nevertheless, treatment with p-Coumaric acid (100 mg/kg b.wt) significantly reverted the altered physical and biochemical parameters back to near normal levels, as evidenced by the histopathology of the ankle joints. In addition, p-Coumaric acid also exhibited potent analgesic and antipyretic effects devoid of any adverse impact on gastric mucosa. The results of this study reveal the potential anti-inflammatory effect of p-Coumaric acid against monosodium urate crystal-induced inflammation in rats.