IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages
| العنوان: | IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages |
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| المؤلفون: | Jianghong Wei, Jinxiu Li, Yi Wang, Guorao Wu, Song Jia, Bin Cheng, Xingxu Huang, Cong-Yi Wang, Ting Yuan, Lei Zhang, Shu Zhang, Fa-Xi Wang, Jianping Zhao, Huilan Zhang, Long-Min Chen, Qilin Yu, Fei Sun, Huiren Lei, Li-Zong Rao, Zhang Lu, Yongjian Xu, Biwen Mo |
| المصدر: | Cell Death Differ |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pulmonary Fibrosis, medicine.medical_treatment, Lung injury, Article, Transforming Growth Factor beta1, Bleomycin, Mice, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Fibrosis, Pulmonary fibrosis, medicine, Animals, Humans, SOCS3, Molecular Biology, Mice, Knockout, business.industry, Suppressor of cytokine signaling 1, Interleukins, Macrophages, Correction, Cell Biology, respiratory system, medicine.disease, M2 Macrophage, respiratory tract diseases, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Cytokine, 030220 oncology & carcinogenesis, Cancer research, Female, Interleukin-4, business, Signal Transduction |
| الوصف: | Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has one of the poorest prognosis. However, the molecular mechanisms underlying IPF progression remain largely unknown. In this study, we determined that IL-24, an IL-20 subfamily cytokine member, was increased both in the serum of IPF patients and the bronchoalveolar lavage fluid (BALF) of mice following bleomycin (BLM)-induced pulmonary fibrosis. As a result, IL-24 deficiency protected mice from BLM-induced lung injury and fibrosis. Specifically, loss of IL-24 significantly attenuated transforming growth factor β1 (TGF-β1) production and reduced M2 macrophage infiltration in the lung of BLM-induced mice. Mechanistically, IL-24 alone did not show a perceptible impact on the induction of M2 macrophages, but it synergized with IL-4 to promote M2 program in macrophages. IL-24 suppressed IL-4-induced expression of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, through which it enhanced signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma (STAT6/PPARγ) signaling, thereby promoting IL-4-induced production of M2 macrophages. Collectively, our data support that IL-24 synergizes with IL-4 to promote macrophage M2 program contributing to the development of pulmonary fibrosis. |
| تدمد: | 1476-5403 1350-9047 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6e25174a97301ac724e7693142120daTest https://doi.org/10.1038/s41418-020-00650-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f6e25174a97301ac724e7693142120da |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765403 13509047 |
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