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Avermectin exerts anti‐inflammatory effect by downregulating the nuclear transcription factor kappa‐B and mitogen‐activated protein kinase activation pathway
Author(s) -
Ci Xinxin,
Li Hongyu,
Yu Qinlei,
Zhang Xuemei,
Yu Lu,
Chen Na,
Song Yu,
Deng Xuming
Publication year - 2009
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2009.00684.x
Subject(s) - p38 mitogen activated protein kinases , kinase , signal transduction , tumor necrosis factor alpha , mitogen activated protein kinase , cytokine , mapk/erk pathway , protein kinase a , microbiology and biotechnology , lipopolysaccharide , biology , chemistry , immunology
Lipopolysaccharide (LPS) can induce mouse macrophages to produce a number of cytokines and other inflammatory mediators. Immunopharmacological studies can provide new information on the immunomodulatory activities of some drugs, including their effect on cytokine productions. For this reason, we first investigated the efficacy of avermectin on cytokine levels induced by LPS in vitro, and we found that avermectin can significantly regulate tumor necrosis factor alpha, interleukin (IL)‐1β and IL‐10, but has no significant effect on IL‐6. We further investigated the effects of the drug on the major signal transduction pathways associated with inflammation: nuclear transcription factor kappa‐B (NF‐κB) and the mitogen‐activated protein (MAP) kinases, extracellular signal regulated kinase, p38 and c‐Jun N‐terminal kinase (JNK). RAW 264.7 cells were pretreated with 0.625, 1.25 or 5 mg/L avermectin 1 h prior to treatment with 1 mg/L LPS. Thirty minutes later, cells were fixed, and NF‐κB activation was measured by immunocytochemical analysis, or cells were collected and MAP‐kinase activation was measured by western blot. Signal transduction studies showed that avermectin significantly inhibits NF‐κB p65 translocation into the nucleus and inhibits JNK and p38 phosphorylation protein expression. Therefore, avermectin may inhibit LPS‐induced production of inflammatory cytokines by blocking NF‐κB and MAP‐kinase in RAW 264.7 cells.