PT - JOURNAL ARTICLE AU - Takehide Fumimori AU - Seiyo Honda AU - Kiyoshi Migita AU - Minako Hamada AU - Taro Yoshimuta AU - Junichi Honda AU - Takaaki Fukuda AU - Ritsu Suzuki AU - Masafumi Gotoh AU - Katsumi Eguchi AU - Hisamichi Aizawa TI - Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid synovial cells. DP - 2004 Mar 01 TA - The Journal of Rheumatology PG - 436--441 VI - 31 IP - 3 4099 - http://www.jrheum.org/content/31/3/436.short 4100 - http://www.jrheum.org/content/31/3/436.full SO - J Rheumatol2004 Mar 01; 31 AB - OBJECTIVE: To investigate whether erythromycin (EM) can suppress the expression of cyclooxygenase-2 (COX-2) in rheumatoid synovial cells, and determine the mechanisms involved. Methods. Synovial tissues were obtained from 25 patients with rheumatoid arthritis (RA). Rheumatoid synovial cells were cultured with or without EM (0.1-1000 nM) in the presence of interleukin 1beta (IL-1beta) for various times. Protein expression of COX-2, and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) were detected by Western blot. COX-2 messenger RNA (mRNA) was detected by RT-PCR. DNA binding activity of nuclear factor kappa B (NF-kB) was detected by ELISA. Results. IL-1beta-stimulated synovial cells expressed COX-2 protein. EM suppressed the IL-1beta-induced COX-2 protein expression in a dose-dependent manner and inhibited IL-1beta-induced p38 MAPK phosphorylation, which was correlated with COX-2 expression in synovial cells. In contrast, EM had no effect on DNA binding activity of NF-kB and ERK1/2 expression. CONCLUSION: Our results indicated that EM downregulated COX-2 expression by inhibiting the p38 MAPK cascade, but had no effect on NF-kB or ERK1/2, in rheumatoid synovial cells.