PPAR-γ inhibits IL-13-induced collagen production in mouse airway fibroblasts.

Abstract

Interleukin-13 (IL-13) plays an important role in extracellular matrix production of airway remodeling in asthma. Activation of PPAR-γ has been shown to inhibit the occurrence of airway fibrosis in asthma, yet it remains unknown whether the effect of PPAR-γ on suppression of airway fibrosis is associated with the inhibition of IL-13 signaling. In the present study, primary cultured airway fibroblasts were stimulated with IL-13, and JAK inhibitor, PDGF receptor blocker and MEK inhibitor were applied to investigate the involvement of these pathways in IL-13-induced collagen production. Our results demonstrate that IL-13 dose- and time-dependently induced collagen production in primary cultured mouse airway fibroblasts; this effect was blocked by inhibition of JAK/STAT6 signal pathway. IL-13 also stimulated JAK/STAT6-dependent PDGF production, elevation of PDGF in turn activated ERK1/2 MAPK and caused collagen production. Activation of PPAR-γ by rosiglitazone reduced IL-13-induced collagen expression by suppression of STAT6-driven PDGF production. Our results indicate that activation of JAK/STAT6 signal and subsequent PDGF generation and ERK1/2 MAPK activation mediate IL-13-induced collagen production in airway fibroblasts. This study suggests that activation of PPAR-γ might be a novel strategy for the treatment of asthma partially by inhibition of airway fibrosis.

• Authors: Jiamei Lu, Lu Liu, Yanting Zhu, Yonghong Zhang, Yuanyuan Wu, Guizuo Wang, Dexin Zhang, Jing Xu, Xinming Xie, Rui Ke, Dong Han, Shaojun Li, Wei Feng, Mei Xie, Yun Liu, Ping Fang, Hongyang Shi, Ping He, Yuan Liu, Xiuzhen Sun, Manxiang Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 737 Pg. 133-9 (Aug 15 2014) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24858619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-13
• PPAR gamma
• Platelet-Derived Growth Factor
• STAT6 Transcription Factor
• Thiazolidinediones
• platelet-derived growth factor A
• Rosiglitazone
• Collagen
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Collagen (biosynthesis)
• Enzyme Activation (drug effects)
• Fibroblasts (cytology, drug effects, enzymology, metabolism)
• Interleukin-13 (pharmacology)
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• PPAR gamma (metabolism)
• Phosphorylation (drug effects)
• Platelet-Derived Growth Factor (biosynthesis)
• Respiratory System (cytology)
• Rosiglitazone
• STAT6 Transcription Factor (metabolism)
• Thiazolidinediones (pharmacology)