title: A small compound that inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production.
abstract: Lipopolysaccharide (LPS) is critically involved in the inflammatory responses via generation of several pro-inflammatory cytokines. Since tumor necrosis factor-alpha (TNF-alpha) is one of the major pro-inflammatory cytokines which is induced by LPS treatment, the development of molecules capable of modulating LPS-induced TNF-alpha production is an issue of concern. We identified a novel synthetic compound that inhibits LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMCs). The active compound SM-7409 inhibited LPS-induced TNF-alpha production in a concentration-dependent manner, showing maximal activity at 5 microM. SM-7409 inhibited LPS-induced TNF-alpha mRNA transcript accumulation and protein expression. We also found that SM-7409 strongly inhibits LPS-induced extracellular signal-regulated protein kinase activity in PBMCs. Moreover, we found that SM-7409 strongly inhibits the LPS-induced other pro-inflammatory cytokines, such as interleukin (IL)-1beta and IL-8 in PBMCs. SM-7409 also dramatically inhibits the LPS-induced TNF-alpha production in neutrophils. Taken together, our results demonstrate that SM-7409 is a synthetic compound that inhibits LPS-induced TNF-alpha production, and thus SM-7409 should be useful for the development of chemotherapies targeting LPS-mediated inflammatory responses.
authors.affiliation: Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan, Republic of Korea.
authors.forename: Jung Im
authors.initials: JI
authors.lastname: Kim
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Kyoung Sun
authors.initials: KS
authors.lastname: Park
authors.forename: Taehoon
authors.initials: T
authors.lastname: Lee
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002087:Butyrates; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; C513340:SM 7409; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases