Jing Yang1, Yun-Zhou Li2, Phillip B Hylemon3, Lu-Yong Zhang4, Hui-Ping Zhou5. 1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China; Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA, 23298, United States. 2. McGuire Veterans Affairs Medical Center, Richmond, VA, 23298, United States. 3. Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA, 23298, United States; McGuire Veterans Affairs Medical Center, Richmond, VA, 23298, United States. 4. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: lyzhang@cpu.edu.cn. 5. Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA, 23298, United States; McGuire Veterans Affairs Medical Center, Richmond, VA, 23298, United States. Electronic address: huiping.zhou@vcuhealth.org.
Abstract
AIM: The aim of this study is to examine the effects of cordycepin (CRD) on LPS-induced inflammatory response in macrophages and further investigate the underlying molecular mechanisms. METHODS: Cultured mouse RAW264.7 macrophages and human THP-1-derived macrophages were used in this study. The mRNA and protein expression levels of cytokine IL-1β, IL-6, TNF-α, and MCP-1 were detected by real time RT-PCR, ELISA and Western blot, respectively. The activation of NOD-Like Receptor Protein 3 (NLRP3) inflammasome was analyzed with Western blot analysis and immunofluorescence staining. The ERK1/2 activation was assessed by Western blot analysis. RESULTS: The results demonstrated that pretreatment with CRD (6.25, 12.5, 25, 50μmol/L) dose-dependently inhibited LPS-induced expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1) and cyclooxygenase 2 (COX-2) in mouse RAW264.7 cells. Similar results were obtained in human THP-1-derived macrophages with CRD. Furthermore, CRD remarkably inhibited LPS-induced activation of the NLRP3 inflammasome and ERK1/2 signaling pathway in RAW264.7 cells. CONCLUSION: CRD exerts anti-inflammatory effects in LPS-induced murine and human macrophages at least in part by inhibiting the activation of NLRP3 inflammasome and ERK1/2 signaling pathway as well as inhibition of COX2-mediated inflammatory response.
AIM: The aim of this study is to examine the effects of cordycepin (CRD) on LPS-induced inflammatory response in macrophages and further investigate the underlying molecular mechanisms. METHODS: Cultured mouse RAW264.7 macrophages and humanTHP-1-derived macrophages were used in this study. The mRNA and protein expression levels of cytokine IL-1β, IL-6, TNF-α, and MCP-1 were detected by real time RT-PCR, ELISA and Western blot, respectively. The activation of NOD-Like Receptor Protein 3 (NLRP3) inflammasome was analyzed with Western blot analysis and immunofluorescence staining. The ERK1/2 activation was assessed by Western blot analysis. RESULTS: The results demonstrated that pretreatment with CRD (6.25, 12.5, 25, 50μmol/L) dose-dependently inhibited LPS-induced expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1) and cyclooxygenase 2 (COX-2) in mouse RAW264.7 cells. Similar results were obtained in humanTHP-1-derived macrophages with CRD. Furthermore, CRD remarkably inhibited LPS-induced activation of the NLRP3 inflammasome and ERK1/2 signaling pathway in RAW264.7 cells. CONCLUSION:CRD exerts anti-inflammatory effects in LPS-induced murine and human macrophages at least in part by inhibiting the activation of NLRP3 inflammasome and ERK1/2 signaling pathway as well as inhibition of COX2-mediated inflammatory response.
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