Erythromycin suppresses the expression of COX-2 in rheumatoid synovial cells

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J Rheumatol. 2004 Mar;31(3):436-41.

Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid

synovial cells.

Fumimori T, Honda S, Migita K, Hamada M, Yoshimuta T, Honda J, Fukuda T,

Suzuki R, Gotoh M, Eguchi K, Aizawa H.

First Department of Internal Medicine, Kurume University School of

Medicine, Kurume, Japan.

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.

PMID: 14994385

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