並列タイトル等S100A9は、骨細胞様細胞においてMAPKsおよびSTAT3シグナル伝達経路を介してIL-6およびRANKLの発現を増加させる
タイトル（掲載誌）BioMed Research International
一般注記Objective: Calprotectin is hetero-complex of S100A8 and S100A9 and mainly secreted from neutrophils, monocytes and chondrocytes in inflammatory condition. Calprotectin binds to RAGE and TLR4, and induces the expression of pro-inflammatory chemokines and cytokines in various cells. Periodontitis is chronic inflammatory disease to lead gingival inflammation and alveolar bone resorption. Calprotectin levels in gingival crevicular fluid of periodontitis patients are higher than healthy patients. In the present study, the effects of S100A8 and S100A9 on the expressions of pro-inflammatory cytokines and bone metabolism related factor in mouse osteocyte like cells (MLO-Y4-A2) were investigated.Design: MLO-Y4-A2 cells were treated with S100A8 and S100A9, and the expressions of RAGE, TLR4, RANKL and several inflammatory cytokines were analyzed by PCR and Western blotting or ELISA methods. To investigate the intracellular signaling pathways, phosphorylation of MAPK and STAT3 was determined by Western blotting, and chemical specific inhibitors and siRNAs were used.Results: Expressions of IL-6 and RANKL were increased by treatment with S100A9 but not S100A8. However, both S100A8 and S100A9 did not changed expression of IL-1β, IL-8 and TNF-α. Although RAGE and TLR4 expressions were not up-regulated by S100A9 treatment, transfection of siRNA for RAGE and TLR4 significantly decreased IL-6 and RANKL expressions. In addition, S100A9 activated p38, ERK and STAT3 signaling pathways, and inhibitors for these factors significantly decreased S100A9 induced IL-6 and RANKL expressions.Conclusions: These results indicated that S100A9 induces IL-6 and RANKL production via engagement with RAGE and TLR4 signalings in osteocytes and suggested that S100A9 may play important roles in the periodontal alveolar bone destruction.
DOIinfo:doi/10.1155/2020/7149408
コレクション（個別）国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
受理日（W3CDTF）2020-06-07T00:39:19+09:00
連携機関・データベース国立国会図書館 : 国立国会図書館デジタルコレクション