IL-17A stimulates the expression of inflammatory cytokines via celecoxib-blocked prostaglandin in MC3T3-E1 cells

Autor: Naoto Suzuki, Akira Nakajima, Akemi Kimura, Noriyoshi Shimizu, Masao Maeno, Yuki Koyama, Narihiro Mitsui, Fan Zhang, Rina Sanuki
Rok vydání: 2010
Předmět:
Zdroj: Archives of Oral Biology. 55:679-688
ISSN: 0003-9969
DOI: 10.1016/j.archoralbio.2010.06.003
Popis: Objective The prostaglandins (PGs) released from osteoblasts can alter the process of bone remodelling. Recently, we showed that compressive force induced the expression of pro-inflammatory cytokine interleukin (IL)-17s and their receptors in osteoblastic MC3T3-E1 cells and that IL-17A was expressed most highly. Consequently, in the current study we examined the effect of IL-17A and/or celecoxib on PGE 2 production and the expression of cyclooxygenases (COXs) and inflammatory cytokines in MC3T3-E1 cells. We also examined the effects of PGE 2 and cyclohexamide on the expression of inflammatory cytokines. Methods Cells were cultured with or without IL-17A (0.1, 1.0, or 10 ng/ml) in the presence or absence of 10 μM celecoxib, a specific inhibitor of COX-2, for up to 72 h. Cells were pretreated with or without 10 μg/ml cycloheximide, protein synthesis inhibitor, for 30 min, and then cultured with 10 ng/ml IL-17A for 24 h. Cells were also cultured with or without 1.5 ng/ml PGE 2 for 24 h. PGE 2 production was determined by ELISA. The expression of COX-1, COX-2, IL-1α, IL-6, IL-8, IL-11, and TNF-α mRNAs and proteins was determined by real-time PCR and ELISA, respectively. Results The expression of COX-2, IL-1α, IL-6, IL-8, IL-11, and TNF-α, as well as PGE 2 production increased in the presence of IL-17A, whereas COX-1 expression did not change. Celecoxib blocked the stimulatory effect of IL-17A on the expression of COX-2, IL-1α, IL-6, IL-8, and IL-11 as well as PGE 2 production, whereas it did not block TNF-α expression. Cycloheximide pretreatment suppressed the expression of IL-17-induced inflammatory cytokines. The expression of IL-1α, IL-6, IL-8, and IL-11 increased by the addition of PGE 2 , whereas TNF-α expression was not affected. Conclusion These results suggest that IL-17A stimulates the expression of bone resorption-related inflammatory cytokines through an autocrine mechanism involving celecoxib-blocked PGs, mainly PGE 2 , in osteoblasts.
Databáze: OpenAIRE