Resveratrol inhibits cytokine production in lpsstimulated RAW264.7 cells potentially through TLR4/MYD88/NF-κB pathway

Resveratrol is a naturally occurring compound with anti-inflammatory properties. However, the protective molecular mechanisms of resveratrol against LPS-induced inflammation have not been thoroughly known. In the present study, we examined the antiinflammatory effect of resveratrol in inflammatory model using murine macrophage-like cell RAW264.7 stimulated with LPS. Resveratrol suppressed the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells with the IC50 value as 17.5 ± 0.7 μM for IL-6, 14.2 ± 1.9 μM for IL-10, and 18.9 ± 0.6 μM for TNF-α.
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Resveratrol inhibits cytokine production in lpsstimulated RAW264.7 cells potentially through TLR4/MYD88/NF-κB pathwayVietnam Journal of Biotechnology 21(4): 611-619, 2023RESVERATROL INHIBITS CYTOKINE PRODUCTION IN LPS-STIMULATED RAW264.7 CELLS POTENTIALLY THROUGHTLR4/MYD88/NF-κB PATHWAYTo Minh Nhat1, Tran Thu Trang2,3, Nguyen Trung Nam2,3,*1 University of Science and Technology of Hanoi, Vietnam Academy of Science andTechnology, 18 Hoang Quoc Viet Road, Cau Giay District, Hanoi, Vietnam2 Graduate University of Science and Technology, Vietnam Academy of Science andTechnology, 18 Hoang Quoc Viet Road, Cau Giay District, Hanoi, Vietnam3 Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang QuocViet Road, Cau Giay District, Hanoi, Vietnam* To whom correspondence should be addressed. E-mail: nam@ibt.ac.vn Received: 25.10.2023 Accepted: 28.11.2023 SUMMARY Resveratrol is a naturally occurring compound with anti-inflammatory properties. However, the protective molecular mechanisms of resveratrol against LPS-induced inflammation have not been thoroughly known. In the present study, we examined the anti- inflammatory effect of resveratrol in inflammatory model using murine macrophage-like cell RAW264.7 stimulated with LPS. Resveratrol suppressed the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells with the IC50 value as 17.5 ± 0.7 μM for IL-6, 14.2 ± 1.9 μM for IL-10, and 18.9 ± 0.6 μM for TNF-α. Gene expression of TLR4, MyD88 and NF-κB were significantly suppressed by resveratrol treatment in LPS- stimulated RAW264.7 cells. In conclusion, the anti-inflammatory property of resveratrol is potentially related to its inhibitory effect on TLR4/MyD88/NF-κB signaling pathway in macrophages. Keywords: Macrophages, inflammatory cytokines, lipopolysaccharide, resveratrolINTRODUCTION pain. During inflammation, white blood cells release substances into the blood or tissues to Inflammation is the spontaneous defense protect the affected tissue/organ injured orresponse of human body tissue to any kind of infected. This required increased blood flowinjury and also a response to stimuli to the areas of injury or infection, resulting inincluding bacteria and viruses that can redness and warmth. Swelling occurs by thepromote the release of inflammatory leakage of fluid into the affected tissue,cytokines from macrophages or dendritic which is caused by some of these compoundscells. The primary indicators of from white blood cells. This protectiveinflammation are redness, heat swelling, and swelling process may trigger nerves to cause 611 To Minh Nhat et al.pain. While acute inflammation is an initial responses and other chronic diseasesresponse of the body to harmful stimuli, (Hayden & Ghosh, 2004). Despite numerouschronic inflammatory response endangers reports indicating that Res can inhibit NF-κBthe body tissue involved. The uncontrolled activation and target gene expressioninflammatory response is involved in various induced by various proinflammatory stimuliimmune diseases (Ahmed, 2011). (Xu et al., 2018), the direct molecular targets Lipopolysaccharides (LPS) in the outer and the mechanisms for such inhibition arewall of Gram-negative bacteria can cause an unknown.inflammatory response by activating the Thus, in this study, we aimed to identifyproduction of inflammatory cytokines in the molecular targets of Res in downstreamdifferent cell types including macrophages signaling pathways activated by LPS-TLR4.(Takashiba et al., 1999; Liang et al., 2013).LPS has been used to examine inflammationbecause of the affluence of the inflammatory MATERIALS AND METHODSeffect, which is generated through Toll-likereceptors 4 (TLR4) signaling pathways. MaterialsTLR4 is a cellular receptor for bacterial LPS, Res was purchased from Sigma (CA,which is by far the most extensively studied USA). RAW264.7 cell line was provided bymember of the TLR family. After being Dr. T. Kishimoto, Osaka University, Japan.activated by LPS, TLR4 signaling has been These cells were cultured in RPMI 1640divided into MyD88-dependent ...