Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes.
Curcumin, a polyphenolic compound derived from plant, regulates heme oxygenase (HO-1) expression within certain cell types; however, the Curcumin-mediated signal transduction in the regulation of HO-1 expression within human monocytes/macrophages is unclear. Herein, we show that Curcumin dose dependently induced HO-1 expression and HO-1 activity through the activation of PKCalpha, PKCdelta/ERK1/2, p38alpha, and PI3-kinase. In addition, H2O2 release is essential for Curcumin-mediated ERK1/2 and p38 phosphorylation and HO-1 expression. Further, Curcumin inhibited LPS-induced IL-1 and IL-6 secretion and blockage of HO-1 expression/activity by HO-1 siRNA or HO-1 inhibitor, SnPP reversed the inhibitory effects of Curcumin on cytokines secretion. HO-1 over-expression produced the same inhibitory effects of Curcumin on IL-1 secretion. Collectively, our results suggest that Curcumin inhibits cytokines secretion within LPS-stimulated monocytes through a mechanism that involves the action of HO-1.
Hsu
Hsien-Yeh
HY
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan. hyhsu@ym.edu.tw
Chu
Li-Chieh
LC
Hua
Kuo-Feng
KF
Chao
Louis Kuoping
LK
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051745:Protein Kinase C-delta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin