Interleukin-19 Aggravates Pulmonary Fibrosis via Activating Fibroblast through TGF-β/Smad Pathway

Abstract

Background. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia disease with no cure. Communication between injured cells is triggered and maintained by a complicated network of cytokines and their receptors. IL-19 is supported by increasing evidences for a deleterious role in respiratory diseases. However, its potential role in lung fibrosis has never been explored. Methods. Bioinformatic, immunohistochemistry and western blot analysis were used to assess the expression of IL-19 in human and mouse fibrosis lung tissues. CCK-8, transwell and flow cytometry assay were utilized to analyze the effect of IL-19 on biological behaviors of lung fibroblasts. Histopathology was used to elucidate profibrotic effect of IL-19 in vivo. Results. IL-19 was upregulated in fibrosis lung tissues. IL-19 promoted lung fibroblasts proliferation and invasion, inhibited cell apoptosis, and induced differentiation of fibroblasts to the myofibroblast phenotype, which could be revised by LY2109761, a TGF-β/Smad signaling pathway inhibitor. Furthermore, we found that IL-19 aggravated lung fibrosis in murine bleomycin-induced lung fibrosis. Conclusions. Our results imply the profibrotic role for IL-19 through direct effects on lung fibroblasts and the potential of targeting IL-19 for therapeutic intervention in pulmonary fibrosis.

A Network Pharmacology and Molecular Dynamics Simulation-Based Study of Qing Run Hua Jie Decoction in Interstitial Pneumonia Treatment

“…Pathologically, IP is a common representative of idiopathic pulmonary fibrosis, and the final feature of IP is pulmonary interstitial fibrosis. 20 Therefore, referring to the previous research methods, 21 the inhibitory effect of drugs on TGF-β1-induced HELF cell fibrosis was explored through HELF cells, which could reflect the mechanism of drugs in IP from a specific perspective. Firstly, we analyzed the effect of changes in luteolin and diosgenin concentration on cell viability by CCK-8 method.…”

Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury

“…The results showed IL-19 is a member of the IL-10 family and is produced primarily by macrophages [16]. IL-19 is expressed in many organs, such as skin [16], lung [34] and intestine [16].…”

“…IL-19 is a member of the IL-10 family and is produced primarily by macrophages [ 16 ]. It is expressed in many organs, such as the skin [ 16 ], lungs [ 34 ], and intestines [ 16 ]. IL-19 expression in the pancreas was confirmed in exocrine glandular cells and mixed immune cells [ 35 ], according to single cell RNA-seq data from the Human Protein Atlas (HPA).…”

Antioxidant therapy against TGF‐β/SMAD pathway involved in organ fibrosis

“… 84 It is evident that Interleukin‐19 (IL‐19) has great anti‐inflammatory properties, especially in vascular diseases, 85 yet, this function is not evident in the case of PF. Combination of wet lab and dry lab techniques has led to this understanding that IL‐19 is elevated in fibrotic lung ( 86 ). It was demonstrated that this cytokine has adverse effects on idiopathic pulmonary fibrosis (IPF) both in vitro and in vivo ( 86 ).…”

“…Combination of wet lab and dry lab techniques has led to this understanding that IL‐19 is elevated in fibrotic lung ( 86 ). It was demonstrated that this cytokine has adverse effects on idiopathic pulmonary fibrosis (IPF) both in vitro and in vivo ( 86 ). Interestingly, all of the mentioned effects are directly reversed by LY2109761, which inhibits TGF‐β/ SMAD signalling pathway ( 86 ).…”