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Erythromycin Suppresses the Expression of Cyclooxygenase-2 in Rheumatoid Synovial Cells
TAKEHIDE FUMIMORI, SEIYO HONDA, KIYOSHI MIGITA, MINAKO HAMADA, TARO YOSHIMUTA, JUNICHI HONDA, TAKAAKI FUKUDA, RITSU SUZUKI, MASAFUMI GOTOH, KATSUMI EGUCHI, and HISAMICHI AIZAWA
ABSTRACT. 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 1ß (IL-1ß) 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-1ß-stimulated synovial cells expressed COX-2 protein. EM suppressed the IL-1ß-induced COX-2 protein expression in a dose-dependent manner and inhibited IL-1ß-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. (J Rheumatol 2004;31:436-41) Key Indexing Terms:
ERYTHROMYCIN
From the First Department of Internal Medicine, Kurume University School of Medicine, Kurume; First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki; and Department of Orthopedic Surgery, Kurume University Medical Center, Kurume, Japan. T. Fumimori, MD; S. Honda, MD, PhD, Kurume University School of Medicine; K. Migita, MD, PhD, Nagasaki University School of Medicine; M. Hamada, MD, PhD; T. Yoshimuta, MD; J. Honda, MD, PhD; T. Fukuda, MD, PhD, Professor, Kurume University School of Medicine; R. Suzuki, MD, PhD; M. Gotoh, MD, PhD, Kurume University Medical Center; K. Eguchi, MD, PhD, Professor; H. Aizawa, MD, PhD, Professor, Kurume University School of Medicine. Address reprint requests to Dr. H. Aizawa, First Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011 Japan. E-mail: aizawa@med.kurume-u.ac.jp Submitted February 14, 2003; revision accepted September 9, 2003. |