期刊
ALLERGOLOGY INTERNATIONAL
卷 68, 期 1, 页码 101-109出版社
JAPANESE SOC ALLERGOLOGY
DOI: 10.1016/j.alit.2018.08.005
关键词
Asthma; Eotaxin-3; Fibroblast; Interleukin-13; Transcriptome
资金
- Japan Society for the Promotion of Science (KAKENHI) [16K18437, 15K09211, 16H02653]
- GSK Japan Research Grant
- Ministry of Health, Labor, and Welfare, Japan
- Grants-in-Aid for Scientific Research [16K18437, 15K09211] Funding Source: KAKEN
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-alpha/beta signaling. Among eight SOCS family members, CISH was most strongly induced by IL-13 via phosphorylation of signal transducer and activator of transcription 6 (STATE). 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. Copyright (C) 2018, Japanese Society of Allergology. Production and hosting by Elsevier B.V.
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