RT Journal Article
SR Electronic
T1 Methotrexate suppresses inflammatory agonist induced interleukin 6 synthesis in osteoblasts.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 787
OP 795
VO 32
IS 5
A1 Minoru Yoshida
A1 Yosuke Kanno
A1 Akira Ishisaki
A1 Haruhiko Tokuda
A1 Kouseki Hirade
A1 Keiichi Nakajima
A1 Yoshihiro Katagiri
A1 Katsuji Shimizu
A1 Osamu Kozawa
YR 2005
UL http://www.jrheum.org/content/32/5/787.abstract
AB OBJECTIVE: Interleukin 6 (IL-6) is a pleiotropic cytokine that plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). In bone metabolism, it is known that IL-6 is produced and secreted by osteoblasts, and that IL-6 induces osteoclast formation and stimulates bone resorption. Various bone inflammatory agonists such as tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, prostaglandin D2 (PGD2), PGE2, and PGF2alpha, which play important roles in the pathogenesis of RA, induce IL-6 synthesis in osteoblast-like MC3T3-E1 cells. Low dose methotrexate (MTX) is currently used for treatment of patients with RA. We investigated the effect of MTX on IL-6 synthesis induced by these agents in MC3T3-E1 cells. METHODS: Cultured cells were pretreated with various doses of MTX, and then stimulated by these inflammatory agonists. The IL-6 in the conditioned medium was measured by IL-6 enzyme immunoassay. RESULTS: MTX significantly suppressed IL-6 synthesis stimulated by these agonists in a dose-dependent manner, although MTX alone had no effect on the levels of IL-6. In addition, MTX significantly inhibited the enhancement by IL-17 of TNF-alpha-stimulated IL-6 synthesis. MTX reduced the levels of IL-6 induced by 12-O-tetradecanoylphorbol 13-acetate, a direct activator of protein kinase C (PKC), suggesting that MTX inhibits PKC signals for IL-6 synthesis. CONCLUSION: MTX suppresses IL-6 synthesis stimulated by various inflammatory agonists in osteoblasts.