Inhibition Of Proinflammatory Cytokine Production Research Articles

Dehydroepiandrosterone Sulfate and Arterial Hypertension

Dehydroepiandrosterone sulfate (DHEAS) is a steroid molecule whose function and mechanism of action in the human body are still inadequately researched. A potential protective function for the cardiovascular system can be explained by activation of nitric oxide production, impact on endothelial and mitochondrial function, and inhibition of proinflammatory cytokine production (IL-6 and TNF-α). Some research shows the beneficial effects of DHEA/DHEAS on many bodily functions, especially in the cardiovascular and the neurological systems. However, we need to be careful with interpretation of the results because of different criteria used for defining arterial hypertension, the race that was observed, and reproductive status of women, as these factors can change the conclusion. Due to a lack of evidence, DHEAS supplementation is still not recommended. We need multicentric prospective and randomized studies on DHEAS to examine its potential impact on blood pressure regulation and cardiovascular risk.

Mechanism of action, resistance, synergism, and clinical implications of azithromycin.

BackgroundAzithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti‐inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide.MethodsSeveral databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies.ResultsAZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections.ConclusionsOur study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed.

Multiple Micronutrient Supplementation: As a Supportive Therapy in the Treatment of COVID-19.

During the infection and treatment of the SARS-CoV-2 viral infection, age and comorbidities play a major role in the successful management of COVID-19. The nutritional status changes which occur in the body vary with the age and underlying conditions and has a vital role in the functioning of the immune system and cellular membrane integrity, thus minimizing the vulnerability to the infection. Considering the data already published by eminent researchers, a few micronutrients have shown outstanding results as supportive therapies in the treatment of viral infections. Micronutrient like zinc improves the membrane barrier integrity, has anti-inflammatory activity, and is involved in antibody production. Vitamin A supports the phagocytic activity of macrophages, while vitamin C reduces the worsening of respiratory tract infections by restoring the dysfunctional epithelial barrier of the lungs. Vitamin D, vitamin E, selenium, and omega-3 fatty acid metabolites play a major role in immunomodulation and in the inhibition of proinflammatory cytokine production. Magnesium is involved in the synthesis of antibodies, while copper, vitamin B12, and folate have significant effects on immune cells. A few researchers suggest that iron supplementation has reduced the risk of acquiring respiratory tract infections in children. As the age of the patient increases, the need for micronutrients increases, thus leading to an imbalanced nutritional status which in turn increases the risk and fatality of the infections. The use of micronutrients in modulating the inflammatory, immune responses, and the epithelial barrier integrity is explored during the treatment of viral infections for faster recovery.

Amelioration of DSS-Induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22.

IL-22, a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The tissue-protective properties of IL-22 are expected to be potentially exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and non-functional oligomers. Monomeric IL-22 (mIL-22) was highly purified through a series of 3 separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate STAT3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model.

Despite antigen affinity of B cells varying from cell to cell, functional analyses of antigen-reactive B cells on individual B cells are missing due to technical difficulties. Especially in the field of autoimmune diseases, promising pathogenic B cells have not been adequately studied to date because of its rarity. In this study, functions of autoantigen-reactive B cells in autoimmune disease were analyzed at the single-cell level. Since topoisomerase I is a distinct autoantigen, we targeted systemic sclerosis as autoimmune disease. Decreased and increased affinities for topoisomerase I of topoisomerase I-reactive B cells led to anti-inflammatory and pro-inflammatory cytokine production associated with the inhibition and development of fibrosis, which is the major symptom of systemic sclerosis. Furthermore, inhibition of pro-inflammatory cytokine production and increased affinity of topoisomerase I-reactive B cells suppressed fibrosis. These results indicate that autoantigen-reactive B cells contribute to the disease manifestations in autoimmune disease through their antigen affinity.

ROCK2 inhibition attenuates profibrogenic immune cell function to reverse thioacetamide-induced liver fibrosis

Background & AimsFibrosis, the primary cause of morbidity in chronic liver disease, is induced by pro-inflammatory cytokines, immune cell infiltrates, and tissue resident cells that drive excessive myofibroblast activation, collagen production, and tissue scarring. Rho-associated kinase 2 (ROCK2) regulates key pro-fibrotic pathways involved in both inflammatory reactions and altered extracellular matrix remodelling, implicating this pathway as a potential therapeutic target.MethodsWe used the thioacetamide-induced liver fibrosis model to examine the efficacy of administration of the selective ROCK2 inhibitor KD025 to prevent or treat liver fibrosis and its impact on immune composition and function.ResultsProphylactic and therapeutic administration of KD025 effectively attenuated thioacetamide-induced liver fibrosis and promoted fibrotic regression. KD025 treatment inhibited liver macrophage tumour necrosis factor production and disrupted the macrophage niche within fibrotic septae. ROCK2 targeting in vitro directly regulated macrophage function through disruption of signal transducer and activator of transcription 3 (STAT3)/cofilin signalling pathways leading to the inhibition of pro-inflammatory cytokine production and macrophage migration. In vivo, KDO25 administration significantly reduced STAT3 phosphorylation and cofilin levels in the liver. Additionally, livers exhibited robust downregulation of immune cell infiltrates and diminished levels of retinoic acid receptor-related orphan receptor gamma (RORγt) and B-cell lymphoma 6 (Bcl6) transcription factors that correlated with a significant reduction in liver IL-17, splenic germinal centre numbers and serum IgG.ConclusionsAs IL-17 and IgG–Fc binding promote pathogenic macrophage differentiation, together our data demonstrate that ROCK2 inhibition prevents and reverses liver fibrosis through direct and indirect effects on macrophage function and highlight the therapeutic potential of ROCK2 inhibition in liver fibrosis.Lay summaryBy using a clinic-ready small-molecule inhibitor, we demonstrate that selective ROCK2 inhibition prevents and reverses hepatic fibrosis through its pleiotropic effects on pro-inflammatory immune cell function. We show that ROCK2 mediates increased IL-17 production, antibody production, and macrophage dysregulation, which together drive fibrogenesis in a model of chemical-induced liver fibrosis. Therefore, in this study, we not only highlight the therapeutic potential of ROCK2 targeting in chronic liver disease but also provide previously undocumented insights into our understanding of cellular and molecular pathways driving the liver fibrosis pathology.

Exosomes from Adipose Tissues Derived Mesenchymal Stem Cells Overexpressing MicroRNA-146a Alleviate Diabetic Osteoporosis in Rats.

Inflammation is one of major contributors of diabetic osteoporosis. Here, we combined adipose tissues derived mesenchymal stem cells (AD-MSCs)-derived exosomes and microRNA-146a (miR-146a) to develop more effective anti-inflammation strategy in osteoclasts. miR-146a was overexpressed in AD-MSCs and miR-146a exosomes (miR-146a-Exo) were isolated and characterized. Cellular and animal diabetic osteoporosis models were created to evaluate the anti-inflammation effect of miR-146a-Exo by using ELISA, qRT-PCR, MTT, bone resorption assay, Western blot, and bone mineral content and density analysis in vitro and in vivo. miR-146a-Exo administration presented the most potent effect on inhibition of pro-inflammatory cytokines production in high glucose-treated osteoclasts, restraint bone resorption, and restoration of the bone loss in streptozotocin-induced diabetic osteoporosis rats. Mechanistically, miR-146a-Exo suppressed the expression of TNF-α, IL-18, and IL-1β, induced the inactivation of inflammasome, and finally reduced bone resorption and recovered bone loss. Combination of AD-MSCs-Exo and miR-146a more effectively exert the anti-inflammation effect in osteoclasts, providing a potential drug for the treatment of diabetic osteoporosis.

5-Hydroxymaltol Derived from Beetroot Juice through Lactobacillus Fermentation Suppresses Inflammatory Effect and Oxidant Stress via Regulating NF-kB, MAPKs Pathway and NRF2/HO-1 Expression

Inflammation is the first response of the immune system against bacterial pathogens. This study isolated and examined an antioxidant derived from Lactobacillus fermentation products using cultured media with 1% beet powder. The antioxidant activity of the beet culture media was significantly high. Antioxidant activity-guided purification and repeated sample isolation yielded an isolated compound, which was identified as 5-hydoxymaltol using nuclear magnetic resonance spectrometry. We examined the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation of macrophages. 5-Hydroxymaltol suppressed nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. It also suppressed tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) in the messenger RNA and protein levels in LPS-treated RAW 264.7 cells. Moreover, it suppressed LPS-induced nuclear translocation of NF-κB (p65) and mitogen-activated protein kinase activation. Furthermore, 5-hydroxymaltol reduced LPS-induced reactive oxygen species (ROS) production as well as increased nuclear factor erythroid 2–related factor 2 and heme oxygenase 1 expression. Overall, this study found that 5-hydroxymaltol has anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophage cells based on its inhibition of pro-inflammatory cytokine production depending on the nuclear factor κB signaling pathway, inhibition of LPS-induced reactive oxygen species production, inhibition of LPS-induced mitogen-activated protein kinase induction, and induction of the nuclear factor erythroid 2–related factor 2/heme oxygenase 1 signaling pathway. Our data showed that 5-hydroxymaltol may be an effective compound for treating inflammation-mediated diseases.

Mannose receptor of Epinephelus coioides exerts antiviral activity against red-spotted grouper nervous necrosis virus and regulates apoptosis and inflammation

Mannose receptor (MR), a pattern recognition receptor, plays a critical role in innate immune responses by binding to pathogen-associated molecular patterns. The antiviral role of MR has been described extensively in mammals but not well characterized in teleosts. In this study, we investigated the role of Epinephelus coioides MR in red spotted grouper nervous necrosis virus (RGNNV) infection by cloning and characterizing EcMR. The sequence analysis showed that EcMR contained a signal peptide, ricin-like β-type clover domain (RICIN), fibronectin type II domain (FN II), eight tandem C-type lectin-like domains (CLECTs), and a transmembrane domain. The function of EcMR was analyzed using constructs expressing three segments of the full-length protein including EcMR1 (RICIN-FN II), EcMR2 (CLECT 1–3), and EcMR3 (CLECT 4–8). Overexpression of EcMR1, EcMR2, and EcMR3 significantly reduced RGNNV coat protein expression at both mRNA and protein levels. Conversely, RGNNV replication was increased by EcMR knockdown. EcMR was found to inhibit apoptosis signaling and inflammation in GF-1 grouper fin cells, as determined by immunofluorescence analysis and flow cytometry. The increases in apoptosis-related gene expression (FADD, Fas, Bax, and p53) and apoptosis-related enzyme activities (caspase-3, −8, and − 9) in cells overexpressing EcMR1, EcMR2, and EcMR3 and the contrary effect observed upon EcMR knockdown indicated that EcMR blocks apoptosis induced by RGNNV. EcMR also exhibited an anti-inflammatory function through suppression of proinflammatory cytokine production. These results demonstrate that EcMR contributes to the response of E. coioides to virus infection by modulating virus-induced apoptosis and inflammation, which may have important implications for commercial aquaculture practices.

Suppression of Lipopolysaccharide-Induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid in RAW 264.7 Macrophages and Zebrafish Larvae.

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19.

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on timing with respect to the disease course. Azithromycin is an immunomodulatory drug that has been shown to have antiviral effects and potential benefit in patients with COVID-19. Multiple immunomodulatory effects have been defined for azithromycin which could provide efficacy during the late stages of the disease, including inhibition of pro-inflammatory cytokine production, inhibition of neutrophil influx, induction of regulatory functions of macrophages, and alterations in autophagy. Here we review the published evidence of these mechanisms along with the current clinical use of azithromycin as an immunomodulatory therapeutic. We then discuss the potential impact of azithromycin on the immune response to COVID-19, as well as caution against immunosuppressive and off-target effects including cardiotoxicity in these patients. While azithromycin has the potential to contribute efficacy, its impact on the COVID-19 immune response requires additional characterization so as to better define its role in individualized therapy.

Cinnamtannin B1 attenuates rosacea-like signs via inhibition of pro-inflammatory cytokine production and down-regulation of the MAPK pathway.

BackgroundRosacea is a common inflammatory disease of facial skin. Dysregulation of innate immunity with enhanced inflammation and increased abundance of LL-37 at the epidermal site is a characteristic feature of rosacea. Cinnamtannin B1 (CB1) is a condensed tannin with anti-inflammatory and anti-microbial activities. The aims of the study were to evaluate the potential of CB1 as a therapy for rosacea and to characterize the potential mechanisms of action.MethodsWe intraperitoneally administered 20 mg/kg CB1 once daily for 2 days into the LL-37-induced mouse model of rosacea. The effects of CB1 in vivo were evaluated by the observations of lesions, histology, immunohistochemistry, and the transcription and translation of pro-inflammatory cytokines and chemokines. Human keratinocyte HaCaT and monocyte THP-1 were used to characterize the effects of CB1 on LL-37-induced inflammation in vitro. The changes in pro-inflammatory chemokine interleukin-8 (IL-8) were quantitated by enzyme-linked immunosorbent assay (ELISA), and the expressions of genes involved were determined by Western blotting.ResultsCB1 attenuated local redness, inflammation, and neutrophil recruitment in the mouse model of rosacea in vivo. CB1 suppressed myeloperoxidase (MPO) and macrophage inflammatory protein 2 (MIP-2) production, a functional homolog of interleukin-8 (IL-8), at the lesions. In vitro experiments confirmed that CB1 reversed the LL-37-induced IL-8 production in human keratinocytes HaCaT and monocyte THP-1 cells. CB1 inhibited IL-8 production through downregulating the phosphorylation of extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinase (MAPK) pathway.ConclusionCB1 attenuated LL-37-induced inflammation, specifically IL-8 production, through inhibiting the phosphorylation of ERK. CB1 has potential as a treatment for rosacea.

The accessory protein ORF3 of porcine epidemic diarrhea virus inhibits cellular interleukin-6 and interleukin-8 productions by blocking the nuclear factor-κB p65 activation

Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded positive-sense RNA virus that belongs to a porcine entero-pathogenic alphacoronavirus, causing lethal watery diarrhea in piglets. Despite existing study reports the sole accessory protein ORF3 identified as NF-κB antagonist, the contribution of PEDV ORF3 to production of the pro-inflammatory cytokines mediated by NF-κB signaling remains largely unknown. Thus in this present study, we showed that PEDV ORF3 protein significantly inhibited the productions of pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8. The phosphorylation of IκBα was inhibited by ORF3 protein, but no degradation of IκBα was induced in ORF3-expressing cells. Furthermore, PEDV ORF3 inhibited NF-κB activation through preventing nuclear factor p65 phosphorylation and down-regulating p65 expression level, as well as interfering nuclear translocation of p65, eventually resulting into the inhibition of IL-6 and IL-8 production. Our study definitely links PEDV ORF3 to inhibition of pro-inflammatory cytokines production, which will provide new insight into the molecular mechanisms of NF-κB activity inhibited by PEDV proteins to facilitate virus evasion of host innate immune.

The Combined Use of Leutragin and Pulmonary Surfactant-BL Increases Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome

This study aims to investigate effects of leutragin — a stabilized analogue of the endogenous hexapeptide dynorphin 1-6 — in combination with pulmonary surfactant-BL on animal survival in an experimental fatal model of “cytokine storm” and acute respiratory distress syndrome (ARDS) in C57Bl/6Y mice. Compared to the control, administration of leutragin and pulmonary surfactant-BL in a combined regimen led to a statistically significant increase in the survival rate and a decrease in the risk of death in animals with ARDS. It was shown that the suppression of proinflammatory cytokine production in the lungs with a simultaneous replenishment of the endogenous surfactant with an exogenous pulmonary surfactant is a promising new pharmacological approach to the treatment of ARDS accompanied by a “cytokine storm”.

Inhibitory Effect of Steamed Soybean Wastewater Against DSS-Induced Intestinal Inflammation in Mice.

This study was performed to examine the beneficial potential of steamed soybean wastewater (SSW), which is generated during the manufacture of fermented soybean products and usually discarded as a by-product. The SSW was found to contain considerable amounts of isoflavones and had concentration-dependent radical scavenging capabilities. Moreover, oral administration of SSW effectively prevented colonic damage induced by dextran sulfate sodium (DSS), based on improvement of morphological and histological features, reduction of oxidative stress indicators, suppression of proinflammatory cytokine production, downregulation of inflammatory marker expression in the colonic tissue, and inhibition of the inflammatory activation of macrophages. It suggests that SSW could prevent intestinal inflammation in humans, although its efficacy should be verified through careful study design in humans. These findings have implications for enhancement of the value-added of SSW and for reduction of wastewater treatment costs incurred by the food industry.

Aligned Expression of IFI16 and STING Genes in RRMS Patients' Blood.

Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. The most common disease phenotype is Relapsing-Remitting MS (RRMS). Beta interferons are the first line of RRMS patients' treatment. Interferon-inducible protein 16 (IFI16) as a DNA sensing molecule and its downstream complex stimulator of interferon genes (STING) play a critical role in the activation of type I interferons. Hence we aimed to evaluate the expression rate of IFI16 and STING in RRMS patients' blood under a different type of IFNβ treatment. In the present study, 99 individuals participated. The participants were divided into 4 groups: 28 control subjects, 25 new cases of RRMS patients, 25 RRMS patients treated with IFNβ-1a (B1a), 21 RRMS patients treated with IFNβ-1b (B1b). The EDTA-treated blood samples were taken and transferred at standard conditions to the Cellular and Molecular Research Center of Shahrekord University of Medical Sciences, RNA was extracted and converted into cDNA. To evaluate the expression of IFI16 and STING, the Real-Time PCR method using SYBR Green/ROX qPCR master mix was performed done. The level of genes expression was measured using 2-ΔΔCt method. The obtained data were analyzed using SPSS v22 software. Comparison of the IFI and STING mRNA expression in blood samples in association with gender and age showed no significant differences (p>0.05). Also, the evaluation of IFI16 mRNA level revealed that the IFI16 genes' expressions were remarkably higher in the new case group compared to the control group, however, STING expression did not show any significant difference. The mRNA levels of IFI16 and STING in IFNβ-treated groups were significantly lower than the new case group (p<0.001). Also, the genes' expressions in both the IFNβ-treated groups were significantly lower compared to the control group (p<0.001). In the assessment of the correlation of IFI16 and STING expressions with age and sex in different research groups, no statistically significant differences were seen (p>0.05). Perhaps the IFNβ therapy decreases the IFI16 and STING expression in a STINGdependent pathway as a negative feedback mechanism for regulation of the immune system and suppression of pro-inflammatory cytokines production. The important role of DNA sensing molecules and STING-dependent pathway in MS gives a new insight into future treatment based on STING-direct therapies.

Effects of Flavonoids and Its Derivatives on Immune Cell Responses

Various pieces of evidence have shown that people who consume foods rich in polyphenolic and flavonoids compounds have a lower incidence of inflammatory, autoimmune diseases and cancer. The study aimed to review the most potent compounds that affect the immune response and diseases associated with it. Publications in PubMed and EmBase, from 1974-2018, and patents form Free patents online, Scifinder, Espacenet and Mendeley in which flavonoids, their semi-synthetic and synthetic derivatives are involved in immunosuppressive or immunostimulatory responses in vitro and in vivo. In vitro, flavonoids and their derivatives inhibit various transcriptional factors, which modulate differentiation, proliferation, activation of immune cells and enhance regulatory T cell generation. Some flavonoids exert anti-inflammatory effects through: Blockade of NF-κB, and NLRP3 inflammasome, inhibition of pro-inflammatory cytokine production, IL-1β, IL-2, IL-6, TNF-α, IL-17A, down regulation of chemokines, and reduction of reactive oxygen and nitrogen species. Nevertheless, several reports have shown that some flavonoids enhance immune response by enhancing: oxygen and nitrogen radicals, antibody production, cytotoxic activity against tumours by increasing activating receptors and down regulating inhibitory receptors. In consequence, flavonoids may be potentially useful for treatment of infectious diseases and cancer. The most potent flavonoids in inflammation that modify immune responses are apigenin, quercetin and Epigallocatechin-3-Gallate (EGCG) although, other compounds are still under study and cannot be excluded. The most relevant patents concerning the use of flavones and other polyphenols were revised. A promising future of these compounds in different therapies is discussed.

Anti-inflammatory effect of water extracts obtained from doenjang in LPS-stimulated RAW 264.7 cells

Abstract The effect of water extracts of doenjang (WED) on cyclooxygenase pathway and cytokine production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells was investigated. WED was fractionated by ultrafiltration into five individual groups of molecular weights. All of the WED fractions significantly inhibited the production of prostaglandin E2 (PGE2) and expression of cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Furthermore, each of the WED fractions significantly decreased production of pro-inflammatory cytokine such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (p<0.05). The fraction between 10 to 30 kDa of WED showed the highest inhibition of pro-inflammatory cytokine production, LPS-induced COX-2 expression and PEG2 production. These results suggest that WED fractions may have the anti-inflammatory effect via the stimulus of COX-2 and TNF-α in LPS-stimulated inflammation in RAW 264.7 cells.

S4ASSOCIATION OF NOREPINEPHRINE TRANSPORTER GENE POLYMORPHISMS WITH SUBJECTIVE AND OBJECTIVE MEASURES OF IMPULSIVITY IN ADULT ATTENTION-DEFICIT/HYPERACTIVITY DISORDER

Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded positive-sense RNA virus that belongs to a porcine entero-pathogenic alphacoronavirus, causing lethal watery diarrhea in piglets. Despite existing study reports the sole accessory protein ORF3 identified as NF-κB antagonist, the contribution of PEDV ORF3 to production of the pro-inflammatory cytokines mediated by NF-κB signaling remains largely unknown. Thus in this present study, we showed that PEDV ORF3 protein significantly inhibited the productions of pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8. The phosphorylation of IκBα was inhibited by ORF3 protein, but no degradation of IκBα was induced in ORF3-expressing cells. Furthermore, PEDV ORF3 inhibited NF-κB activation through preventing nuclear factor p65 phosphorylation and down-regulating p65 expression level, as well as interfering nuclear translocation of p65, eventually resulting into the inhibition of IL-6 and IL-8 production. Our study definitely links PEDV ORF3 to inhibition of pro-inflammatory cytokines production, which will provide new insight into the molecular mechanisms of NF-κB activity inhibited by PEDV proteins to facilitate virus evasion of host innate immune.

Isorhamnetin ameliorates inflammatory responses and articular cartilage damage in the rats of monosodium iodoacetate-induced osteoarthritis

Context: Osteoarthritis (OA) is a degenerative joint disease with damage to the articular cartilage. Active production of inflammatory cytokine/chemokine and matrix metalloproteinases may be found during the progression of OA. Isorhamnetin had the effects of anti-inflammatory, antioxidant, anti-ischemia, anti-atherosclerotic hepatoprotective and anticancer activities.Objective: Our study was focused on the effects of isorhamnetin treatment in OA.Materials and methods: We used monosodium iodoacetate (MIA)-induced OA rats to evaluate the effects of isorhamnetin related anti-inflammatory process. The rats in all groups were sacrificed on four weeks post-MIA injection. The measurements of knee joint swelling, histological analysis, serum inflammatory biomarkers and western blot were evaluated.Results: We found that isorhamnetin may reduce MIA-induced knee swelling by significantly reduction of articular cartilage damage.in rats. Suppression of pro-inflammatory cytokines production was found after isohamnetin treatment. Isorhamnetin inhibited the production of NO and PGE2, and the expression of iNOS and COX-2. The production of COMP, CTX-II and osteopontin (OPN) were also inhibited in MIA-induced OA rats.Discussion and conclusions: Isorhamnetin may modulate the inflammatory progression of OA in MIA-induced OA rats. The prevention of cartilage damage was found in OA after adequate isorhamnetin treatment. Isorhamnetin may serve as a potential agent for the management of OA.