論文 - 詳細
RRC ID | 52108 |
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著者 | Komiya K, Ohta S, Arima K, Ogawa M, Suzuki S, Mitamura Y, Nunomura S, Nanri Y, Yoshihara T, Kawaguchi A, Kadota JI, Rubin BK, Izuhara K. |
タイトル | Clarithromycin attenuates IL-13-induced periostin production in human lung fibroblasts. |
ジャーナル | Respir Res |
Abstract |
BACKGROUND:Periostin is a biomarker indicating the presence of type 2 inflammation and submucosal fibrosis; serum periostin levels have been associated with asthma severity. Macrolides have immunomodulatory effects and are considered a potential therapy for patients with severe asthma. Therefore, we investigated whether macrolides can also modulate pulmonary periostin production. METHODS:Using quantitative PCR and ELISA, we measured periostin production in human lung fibroblasts stimulated by interleukin-13 (IL-13) in the presence of two 14-member-ring macrolides-clarithromycin or erythromycin-or a 16-member-ring macrolide, josamycin. Phosphorylation of signal transducers and activators of transcription 6 (STAT6), downstream of IL-13 signaling, was evaluated by Western blotting. Changes in global gene expression profile induced by IL-13 and/or clarithromycin were assessed by DNA microarray analysis. RESULTS:Clarithromycin and erythromycin, but not josamycin, inhibited IL-13-stimulated periostin production. The inhibitory effects of clarithromycin were stronger than those of erythromycin. Clarithromycin significantly attenuated STAT6 phosphorylation induced by IL-13. Global gene expression analyses demonstrated that IL-13 increased mRNA expression of 454 genes more than 4-fold, while decreasing its expression in 390 of these genes (85.9%), mainly "extracellular," "plasma membrane," or "defense response" genes. On the other hand, clarithromycin suppressed 9.8% of the genes in the absence of IL-13. Clarithromycin primarily attenuated the gene expression of extracellular matrix protein, including periostin, especially after IL-13. CONCLUSIONS:Clarithromycin suppressed IL-13-induced periostin production in human lung fibroblasts, in part by inhibiting STAT6 phosphorylation. This suggests a novel mechanism of the immunomodulatory effect of clarithromycin in asthmatic airway inflammation and fibrosis. |
巻・号 | 18(1) |
ページ | 37 |
公開日 | 2017-2-20 |
DOI | 10.1186/s12931-017-0519-8 |
PII | 10.1186/s12931-017-0519-8 |
PMID | 28219384 |
PMC | PMC5319114 |
MeSH | Cell Adhesion Molecules / biosynthesis* Cell Line Clarithromycin / administration & dosage* Dose-Response Relationship, Drug Down-Regulation / drug effects Down-Regulation / physiology Drug Interactions Fibroblasts / drug effects Fibroblasts / metabolism* Humans Interleukin-13 / administration & dosage* Lung / cytology Lung / drug effects Lung / metabolism* |
IF | 3.924 |
引用数 | 7 |
リソース情報 | |
ヒト・動物細胞 | MRC-5(RCB0211) |