Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid synovial cells.
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.


CONCLUSIONS
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.
First Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Takehide
T
Fumimori
Seiyo
S
Honda
Kiyoshi
K
Migita
Minako
M
Hamada
Taro
T
Yoshimuta
Junichi
J
Honda
Takaaki
T
Fukuda
Ritsu
R
Suzuki
Masafumi
M
Gotoh
Katsumi
K
Eguchi
Hisamichi
H
Aizawa
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D004917:Erythromycin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases