title: Curcumin decreases toll-like receptor-2 gene expression and function in human monocytes and neutrophils.
abstract: Toll-like receptor-2 (TLR2) is a pattern recognition receptor that senses many types of bacterial components and activates signaling pathways that induce inflammatory cytokines. A hyperresponsiveness to pathogens caused by increased expression of TLR2 triggers exaggeration of some inflammatory diseases. Here, we showed that curcumin, a well-known anti-inflammatory agent derived from the curry spice turmeric, inhibits TLR2 expression in various TLR2-expressing innate immune cell lines such as monocytic THP-1 cells, neutrophilic-differentiated HL-60 cells. Strong suppression of TLR2 gene expression was specifically observed at concentrations of curcumin in the range 40-100muM. Consistent with decreased expression of TLR2 mRNA, protein expression and ligand-responsiveness of TLR2 were markedly reduced by curcumin treatment. Moreover, curcumin-dependent down-regulation of TLR2 expression and function was also observed in primary peripheral blood monocytes (MC) and polymorphonuclear neutrophils (PMN). Finally, we determined the importance of curcumin-dependent radical generation for the suppressive effect of curcumin on TLR2 expression. Thus, our data demonstrate that curcumin inhibits TLR2 gene expression and function possibly via an oxidative process.
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Global COE "Cell Fate Regulation Research and Education Unit", Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shuto
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ono
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohira
authors.forename: Shogo
authors.initials: S
authors.lastname: Shimasaki
authors.forename: Shota
authors.initials: S
authors.lastname: Mizunoe
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Suico
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Koga
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Saori
authors.initials: S
authors.lastname: Morino
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress; D014176:Protein Biosynthesis / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051195:Toll-Like Receptor 2; D003474:Curcumin