title: Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.
abstract: We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway.
authors.affiliation: College of Medicine, Konkuk University, Korea.
authors.forename: Se Hwan
authors.initials: SH
authors.lastname: Mun
authors.forename: Hyuk Soon
authors.initials: HS
authors.lastname: Kim
authors.forename: Jie Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Na Young
authors.initials: NY
authors.lastname: Ko
authors.forename: Do Kyun
authors.initials: DK
authors.lastname: Kim
authors.forename: Beob Yi
authors.initials: BY
authors.lastname: Lee
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Won
authors.forename: Hwa-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
authors.forename: Hoi Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007596:Joints / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D051379:Mice; D008811:Mice, Inbred DBA; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000166:cytology / Q000473:pathology
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D051745:Protein Kinase C-delta; D048031:JNK Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D003474:Curcumin