Curcumin decreases toll-like receptor-2 gene expression and function in human monocytes and neutrophils.
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.
Shuto
Tsuyoshi
T
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.
Ono
Tomomi
T
Ohira
Yuko
Y
Shimasaki
Shogo
S
Mizunoe
Shota
S
Watanabe
Kenji
K
Suico
Mary Ann
MA
Koga
Tomoaki
T
Sato
Takashi
T
Morino
Saori
S
Sato
Keizo
K
Kai
Hirofumi
H
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051195:Toll-Like Receptor 2; D003474:Curcumin