Korean J Physiol Pharmacol.
2003 Dec;7(6):363-368.
Caffeic Acid Phenethyl Ester Inhibits the PKC-Induced IL-6 Gene Expression in the Synoviocytes of Rheumatoid Arthritis Patients
- Affiliations
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- 1Department of Pharmacology, College of Medicine, Chungnam National University, Daejon 301-747, South Korea. jhseok@cnu.ac.kr
- 2Cancer Research Institute, Chungnam National University, Daejon 301-747, South Korea.
Abstract
- To gain insight on the role of pro-inflammatory cytokines in the pathogenesis and treatment of rheumatoid arthritis (RA), the phorbol 12-myristate 13-acetate (PMA) -induced IL-6 gene expression and the effect of caffeic acid phenethyl ester (CAPE) on the PMA-induced IL-6 gene expression were investigated in human fibroblast-like synoviocytes (FLSs). Synovial tissue samples were obtained from rheumatoid arthritis patients, and FLSs were isolated. The cells were stimulated with PMA (100 nM) for 6 hrs to induce IL-6 gene. The cells were pretreated with CAPE (20, 50, 100 microM) prior to PMA treatment. PMA increased IL-6 RNA expression, binding activities of transcription factors (NF-kappaB, AP-1) to IL-6 promoter, and IL-6 promoter activity. However, CAPE inhibited PMA-induced IL-6 mRNA expression in dose-dependent manner, and also inhibited the increased binding activities of transcription factors to IL-6 promoter and IL-6 promoter activity. These results suggest that CAPE might regulate PKC-mediated IL-6 expression and inflammatory reactions in RA.