IL33/ST2 contributes to airway remodeling via p-JNK MAPK/STAT3 signaling pathway in OVA-induced allergic airway inflammation in mice

Exp Lung Res. 2019 Apr-May;45(3-4):65-75. doi: 10.1080/01902148.2019.1611972. Epub 2019 May 21.

Abstract

Aim of this study: Airway remodeling, which encompasses structural changes in airway is a main feature of asthma. Interleukin-33 (IL-33) has been reported to be a vital cytokine in airway remodeling in asthma, but the underlying mechanisms are not clear yet. This study focused on discussing the role of IL-33 in airway remodeling in asthma. Material and methods: Female BALB/c mice were divided into a control group, an OVA induced allergic airway disease group and an anti-ST2 antibody intervention group. Immunohistochemistry and western blot were performed to detect IL-33, ST2 expression in addition to airway remodeling markers a-smooth muscle actin (a-SMA) and type 1 collagen in OVA-induced mice model. Levels of p-JNK and p-STAT3 activation in mice were detected by western blot. Human lung fibroblast (HLF) were stimulated with rhIL-33, anti-ST2 antibody and JNK inhibitor sp600125 and levels of JNK and STAT3 activation were determined via western blot and immunofluorescence staining. Results: Anti-ST2 treatment inhibited JNK/STAT3 phosphorylation and airway remodeling in OVA-induced mouse model. IL-33 induced a-SMA and collagen 1 expression was inhibited by anti-ST2 antibody and sp600125 treatment via decreased JNK/STAT3 phosphorylation in human lung fibroblast. Conclusions: IL-33 promoted airway remodeling by interacting with ST2 to activate the JNK/STAT3 signaling pathway in asthma.

Keywords: Airway remodeling; Asthma; IL-33; JNK-STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Remodeling*
  • Animals
  • Asthma / chemically induced
  • Asthma / etiology
  • Asthma / metabolism*
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein / metabolism*
  • Interleukin-33 / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lung / pathology
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism*

Substances

  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Ovalbumin
  • JNK Mitogen-Activated Protein Kinases