Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in macrophages

Innate immunity

article

Yunjuan Nie¹  Yudong Hu²  Kaikai Yu²  Dan Zhang³  Yinze Shi¹  Yaolin Li¹  Lei Sun²  Feng Qian² 

[1]Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University

[2]Engineering Research Center of Cell and Therapeutic Ab, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University

[3]Research Center for Cancer Precision Medicine, Bengbu Medical College

关键词: Akt1;    pulmonary fibrosis;    inflammation;    macrophage;    IL-13;   

DOI  :  10.1177/1753425919861774

来源: Sage Journals

【 摘 要 】

Idiopathic pulmonary fibrosis is a progressive interstitial pneumonia characterised by fibroblast accumulation, collagen deposition and extracellular matrix (ECM) remodelling. It was reported that Akt1 mediated idiopathic pulmonary fibrosis progression through regulating the apoptosis of alveolar macrophage, while its effect on macrophage-produced cytokines remains largely unknown. In the present study, we first examined the phosphorylation of Akt1 in lung sections from idiopathic pulmonary fibrosis patients by immunohistochemistry before applying a bleomycin-induced idiopathic pulmonary fibrosis model using Akt1 −/− mice and Akt1 +/+ littermates. The results showed that Akt1 was remarkably up-regulated in idiopathic pulmonary fibrosis patients, while in vivo studies revealed that Akt1-deficient mice had well-preserved alveolar structure and fewer collagens, secreted fewer matrix components, including alpha smooth-muscle actin and fibronectin and survived significantly longer than Akt1 +/+ littermates. Additionally, the pro-fibrogenic cytokine IL-13 was down-regulated at least twofold in Akt1 −/− mice compared to the Akt1 +/+ group on d 3 and 7 after bleomycin treatment. Furthermore, it was found that Akt1 –/– macrophages displayed down-regulation of IL-13 compared to Akt1 +/+ macrophages in which Akt1 was phosphorylated in response to IL-33 stimulation. These findings indicate that Akt1 modulates pulmonary fibrosis through inducing IL-13 production by macrophages, suggesting that targeting Akt1 may simultaneously block the fibrogenic processes of idiopathic pulmonary fibrosis.

【 授权许可】

CC BY|CC BY-NC