Oral Administration of Curcumin Suppresses Production of Matrix Metalloproteinase (MMP)-1 and MMP-3 to Ameliorate Collagen-Induced Arthritis: Inhibition of the PKCδ/JNK/c-Jun Pathway

Se Hwan Mun; Hyuk Soon Kim; Jie Wan Kim; Na Young Ko; Do Kyun Kim; Beob Yi Lee; Bokyung Kim; Hyung Sik Won; Hwa-Sup Shin; Jeung-Whan Han; Hoi Young Lee; Young Mi Kim; Wahn Soo Choi

doi:10.1254/jphs.09134FP

Full Papers

Oral Administration of Curcumin Suppresses Production of Matrix Metalloproteinase (MMP)-1 and MMP-3 to Ameliorate Collagen-Induced Arthritis: Inhibition of the PKCδ/JNK/c-Jun Pathway

Se Hwan Mun, Hyuk Soon Kim, Jie Wan Kim, Na Young Ko, Do Kyun Kim, Beob Yi Lee, Bokyung Kim, Hyung Sik Won, Hwa-Sup Shin, Jeung-Whan Han, Hoi Young Lee, Young Mi Kim, Wahn Soo Choi

Author information

Se Hwan Mun
College of Medicine, Konkuk University, Korea
Hyuk Soon Kim
College of Medicine, Konkuk University, Korea
Jie Wan Kim
College of Medicine, Konkuk University, Korea
Na Young Ko
College of Medicine, Konkuk University, Korea
Do Kyun Kim
College of Medicine, Konkuk University, Korea
Beob Yi Lee
College of Medicine, Konkuk University, Korea
Bokyung Kim
College of Medicine, Konkuk University, Korea
Hyung Sik Won
College of Biomedical & Health Science, Konkuk University, Korea
Hwa-Sup Shin
College of Biomedical & Health Science, Konkuk University, Korea
Jeung-Whan Han
College of Pharmacy, Sungkyunkwan University, Korea
Hoi Young Lee
College of Medicine, Konyang University, Korea
Young Mi Kim
College of Pharmacy, Duksung Women’s University, Korea
Wahn Soo Choi
College of Medicine, Konkuk University, Korea

Keywords: curcumin, matrix metalloproteinase (MMP)-1, MMP-3, protein kinase Cδ (PKCδ), collagen-induced arthritis

JOURNAL FREE ACCESS

2009 Volume 111 Issue 1 Pages 13-21

DOI https://doi.org/10.1254/jphs.09134FP

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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)-α–stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cδ (PKCδ) 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 PKCδ and the JNK/c-Jun signaling pathway.

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