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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-8-27
pubmed:abstractText
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)-1beta 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-kappaB) 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-kappaB 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-kappaB 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-kappaB and MAP-kinase in RAW 264.7 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1472-8206
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
449-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway.
pubmed:affiliation
Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't