- 著者
- Hideyuki Takeshima Masafumi Horie Yu Mikami Kosuke Makita Naoya Miyashita Hirotaka Matsuzaki Satoshi Noguchi Hirokazu Urushiyama Yoshihisa Hiraishi Akihisa Mitani Zea Borok Takahide Nagase Yasuhiro Yamauchi
- 出版者
- Japanese Society of Allergology
- 雑誌
- Allergology International (ISSN:13238930)
- 巻号頁・発行日
- vol.68, no.1, pp.101-109, 2019 (Released:2019-01-26)
- 参考文献数
- 47
- 被引用文献数
- 14
Background: Bronchial asthma is a chronic airway disease characterized by eosinophilic airway inflammation. Lung fibroblasts activated by IL-13 serve as important sources of chemokines, such as eotaxins, contributing to persistent eosinophilic inflammation. Src-homology 2-containing protein (CISH), belonging to the suppressor of cytokine signaling (SOCS) family, acts as a negative regulator of cytokine induction. The aim of this study was to elucidate the role of CISH in the production of eosinophil chemotactic chemokines in human lung fibroblasts.Methods: Normal human lung fibroblasts were stimulated by IL-13, and global gene expression profile was assessed by cDNA microarray. Expression changes and downstream of IL-13 signaling were evaluated by quantitative RT-PCR, ELISA or western blotting. Loss- and gain-of-function analyses of CISH were performed by small interfering RNA and vector overexpression, respectively.Results: Ingenuity pathway analysis revealed that IL-13 induced chemokine signaling, including the eotaxin family, while significantly suppressing IFN-α/β signaling. Among eight SOCS family members, CISH was most strongly induced by IL-13 via phosphorylation of signal transducer and activator of transcription 6 (STAT6). Loss- and gain-of-function studies demonstrated that CISH negatively regulated the expression of CCL26.Conclusions: These findings suggest that CISH plays a key role in the eosinophilic inflammation associated with bronchial asthma by regulating IL-13-induced CCL26 production. Augmentation of CISH function could be a novel approach for treating eosinophilic inflammation in severe asthma.