Altered gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine levels in lung tissue of obese ovalbumin-sensitized rats

Life Sci. 2022 May 1:296:120425. doi: 10.1016/j.lfs.2022.120425. Epub 2022 Feb 22.

Abstract

Aims: The association between asthma and obesity has been shown but its accurate mechanism is unknown. In the current study, we sought to investigate the gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine level (IL-6, IL-1β, and TNF-α) in obese Ovalbumin (OVA)-sensitized female and male Wistar rats lung tissue.

Main methods: Animals in both males and females were divided into eight groups (four groups in each sex) based on diet and OVA-sensitization: normal diet, a normal diet with OVA-sensitization, high-fat diet (HFD), and OVA-sensitization with an HFD.

Key findings: In both sexes, obese OVA-sensitized rats, the methacholine concentration-response curve shifted to the left and EC50 methacholine decreased. Increased pro-inflammatory cytokines as well as elevated IL-17/TRAF6/MAPK axis genes and decreased USP25 gene expression were identified in obese OVA-sensitized groups.

Significance: The results indicate that in obese OVA-sensitized rats, the IL-17 axis were involved in the pathogenesis of the disease and can be considered as a therapeutic target in subjects with obesity-related asthma.

Keywords: Asthma; IL-17A; IL-17F; MAPK; Obesity; TRAF6; USP25.

MeSH terms

  • Animals
  • Body Weight / genetics
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation
  • Interleukin-17 / genetics*
  • Lung / physiology*
  • Lung / physiopathology
  • Male
  • Methacholine Chloride / pharmacology
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Obesity / genetics*
  • Obesity / physiopathology
  • Ovalbumin / toxicity
  • Rats
  • Rats, Wistar
  • TNF Receptor-Associated Factor 6 / genetics*
  • Trachea / drug effects
  • Ubiquitin Thiolesterase / genetics*

Substances

  • Cytokines
  • Il17a protein, rat
  • Interleukin-17
  • TNF Receptor-Associated Factor 6
  • Methacholine Chloride
  • Ovalbumin
  • Mitogen-Activated Protein Kinase Kinases
  • Ubiquitin Thiolesterase