• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.124-129
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• 2005

Pro-inflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin-12 (IL-12) and interleukin $(IL-1)-{\beta}$, play a key role in causing inflammatory diseases, which are rheumatoid arthritis, Crohn's disease and sepsis. Accumulating evidences suggest that low level laser irradiation (LLLI) may have an anti-inflammatory action. However, there are few data regarding down regulation of Th1 immune response by using the diod typed laser emitting device for human patients. As a fundamental step in order to address this issue, we investigated immunological impact of the low level laser irradiation (10 mw laser diode with a wavelength of 630 nm) on expression of pro-inflammatory cytokines in murine immunocytes (splenocytes and peritoneal macrophages) in vitro. The LLLI on lipopolysaccharide (LPS 100 ng/ml)-stimulated murine splenocytes and macrophages, clearly down regulated mRNA expression of $TNF-{\alpha}$ and IL-12 in dose-dependent manner. In addition, LLLI significantly inhibits the NO production in the LPS-stimulated murine macrophages. This data suggests that LLLI (wavelength of 630 nm) may exert an anti-inflammatory action via modulation of pro-inflammatory cytokine and NO production pathway.

• Molecules and Cells
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• v.44 no.5
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• pp.318-327
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• 2021

CD4+ T helper (Th) cells play a crucial role in the modulation of innate and adaptive immune responses through the differentiation of Th precursor cells into several subsets, including Th1, Th2, Th17, and regulatory T (Treg) cells. Effector Th and Treg cells are distinguished by the production of signature cytokines and are important for eliminating intracellular and extracellular pathogens and maintaining immune homeostasis. Stimulation of naive Th cells by T cell receptor and specific cytokines activates master transcription factors and induces lineage specification during the differentiation of Th cells. The master transcription factors directly activate the transcription of signature cytokine genes and also undergo post-translational modifications to fine-tune cytokine production and maintain immune balance through cross-regulation with each other. This review highlights the post-translational modifications of master transcription factors that control the differentiation of effector Th and Treg cells and provides additional insights on the immune regulation mediated by protein argininemodifying enzymes in effector Th cells.

• BMB Reports
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• v.48 no.5
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• pp.239-240
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• 2015

Dysregulation of cytokine expression causes inflammatory diseases or chronic infection conditions. We have identified that Tat-activating regulatory DNA-binding protein-43 (TDP-43) is involved in cytokine RNA processing in order to promote an optimal immune response. The interaction of TDP-43 with spliceosomal components from the Cajal body leads to the formation of a novel sub-nuclear body called the Interleukin (IL)-6 and IL-10 Splicing Activating Compartment (InSAC). TDP-43 binds to the IL-6 and IL-10 RNAs in a sequence-dependent manner. In cell-based studies, we observed that lipopoly-saccharide (LPS) stimulation induces the formation of the InSAC through TDP-43 ubiquitination, thereby influencing the processing and expression levels of IL-6 RNA. Moreover, TDP-43 knockdown in vivo results in a decrease in IL-6 production and its RNA splicing and stability. Thus, these findings demonstrate that the InSAC is linked to the activation and modulation of the immune response. [BMB Reports 2015; 48(5): 239-240]

• Genomics & Informatics
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• v.20 no.3
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• pp.32.1-32.15
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• 2022

Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.

• Mycobiology
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• v.43 no.4
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• pp.450-457
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• 2015

Medicinal mushrooms have been used worldwide to treat cancer and modulate the immune system. Over the last several years, there has been increasing interest in isolating bioactive compounds from medicinal mushrooms and evaluating their health beneficial effects. Fomes fomentarius is used in traditional oriental medicine and is known to possess antioxidant, antiinflammatory, antidiabetic, and antitumor effects. In the present study, we isolated fomentariol from Fomes fomentarius and investigated its anti-inflammatory effect in murine macrophages (RAW264.7 cells) stimulated with lipopolysaccharides. Fomentariol inhibited the production of nitric oxide and intracellular reactive oxygen species triggered by lipopolysaccharides. Interestingly, fomentariol differentially regulated cytokine production triggered by lipopolysaccharides. Fomentariol effectively suppressed the production of interleukin-$1{\beta}$ and interleukin-6 but not tumor necrosis factor-${\alpha}$. The inhibitory effect of fomentariol against nitric oxide, interleukin-$1{\beta}$, and interleukin-6 production was possibly mediated by downregulation of the extracellular signal-regulated kinase signaling pathway. Taken together, our results suggest that fomentariol differentially modulated inflammatory responses triggered by lipopolysaccharides in macrophages and is one of the bioactive compounds that mediate the physiological effects of Fomes fomentarius.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.2878-2882
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• 2012

Amentoflavone is naturally occurring bioflavonoid that is found in a number of plants. In this paper, the anti-inflammatory activity of amentoflavone in LPS-stimulated macrophages and its mode of action were examined. Using LPS-stimulated RAW264.7 macrophage cells, we found that amentoflavone exerted anti-inflammatory activities through inhibition of nitric oxide (NO) production and tumor necrosis factor (TNF)-${\alpha}$ and macrophage inflammatory protein (MIP)-2 secretion. Amentoflavone (1.0-20 ${\mu}M$) gradually inhibited nitrite production without cytotoxicity. Amentoflavone (1.0 and 10 ${\mu}M$) effectively suppressed both TNF-${\alpha}$ and MIP-2 cytokine release from LPS-stimulated RAW264.7 cells. The expression of mIL-$1{\beta}$ and mMIP-2 cytokine mRNAs was completely inhibited while expression of mMIP-1 was effectively suppressed and mTNF-${\alpha}$ expression was slightly inhibited by 10 ${\mu}M$ amentoflavone. We also demonstrated that the innate immune response to amentoflavone involves the toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) pathways. LPS-induced upregulation of p38 MAPK phosphorylation was significantly reduced by 10 ${\mu}M$ amentoflavone. These results suggest that amentoflavone exhibits effective anti-inflammatory activities through regulation of TLR4 and phosphorylation of p38 MAPKs.

• Korean Journal of Agricultural Science
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• v.45 no.4
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• pp.769-777
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• 2018

The fermentation of Panax ginseng yields many compounds including ginsenosides that have various biological functions. The objective of this study was to investigate the modulation of nitric oxide (NO), Interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$ in Raw 264.7 cells treated with ginseng fermented by Penibacillus MBT213. Nitric oxide production in the Raw 264.7 cells treated for 24 hours with fermented ginseng at 3, 7, and 14 days after the treatment decreased to 74, 43, and 36%, respectively, compared with the positive control. The production of IL-6 was inhibited in all the cells treated with fermented ginseng at 3, 7, and 14 days after the treatment except for the positive control. The $TNF-{\alpha}$ production in the Raw 264.7 cells treated with fermented ginseng for 6 hours at 3, 7, and 14 days after the treatment was about 40,000, 85,000 and 65,000 pg/mL, respectively. Moreover, the $TNF-{\alpha}$ production in the Raw 264.7 cells treated with fermented ginseng for 24 hours at 7 and 14 days after the treatment was about 160,000 and 180,000 pg/mL, respectively. However, $TNF-{\alpha}$ production was inhibited in the Raw 264.7 cells at 6 and 12 hours after the treatment with fermented ginseng. herefore, it was confirmed that the immunological activity of the Raw 264.7 macrophages was affected by the treatment with fermented ginseng. It was concluded that ginseng fermented by Paenibacillus MBT213 possesses a potential anti-inflammatory activity and could be used as an ingredient in functional foods and pharmaceutical products.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.922-927
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• 2005

In the present study, baicalin, baicalein, and wogonin, a major flavone isolated from Scutellaria Radix were examined for their effects on PMA-induced Interlukin-6 (IL-6), $interferon-\gamma(IFN-\gamma)$, tumor necrosis factor $(TNF)-\alpha$, IL-4, IL-10, and IL-13 productions in the PMA-stimulated $CD4^+$ Jurkat T cells. These three compounds inhibited PMA-induced Th1 cytokine $(IL-6,\;IFN-\gamma,\;TNF-\alpha)$ and Th2 cytokine (IL-4 and IL-13) productions in a concentration-dependent manner. But wogonin, but not baicalin baicalein, increased PMA-induced IL-10 production. These results suggest that baicalin, baicalein, and wogonin, a major flavone modulate Th1 and Th2 cytokine productions in $CD4^+$ Jurkat T cells and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.27-39
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• 2023

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

• Journal of Veterinary Science
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• v.19 no.6
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• pp.744-749
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• 2018

Dapsone, an antibiotic, has been used to cure leprosy. It has been reported that dapsone has anti-inflammatory activity in hosts; however, the anti-inflammatory mechanism of dapsone has not been fully elucidated. The present study investigated the anti-inflammatory effects of dapsone on bone marrow cells (BMs), especially upon exposure to lipopolysaccharide (LPS). We treated BMs with LPS and dapsone, and the treated cells underwent cellular activity assay, flow cytometry analysis, cytokine production assessment, and reactive oxygen species assay. LPS distinctly activated BMs with several characteristics including high cellular activity, granulocyte changes, and tumor necrosis factor alpha ($TNF-{\alpha}$) production increases. Interestingly, dapsone modulated the inflammatory cells, including granulocytes in LPS-treated BMs, by inducing cell death. While the percentage of Gr-1 positive cells was 57% in control cells, LPS increased that to 75%, and LPS plus dapsone decreased it to 64%. Furthermore, dapsone decreased the mitochondrial membrane potential of LPS-treated BMs. At a low concentration ($25{\mu}g/mL$), dapsone significantly decreased the production of $TNF-{\alpha}$ in LPS-treated BMs by 54%. This study confirmed that dapsone has anti-inflammatory effects on LPS-mediated inflammation via modulation of the number and function of inflammatory cells, providing new and useful information for clinicians and researchers.