Augmented Responses to Ozone in Obese Mice Require IL-17A and Gastrin-Releasing Peptide.

Published

Journal Article

Ozone and obesity both increase IL-17A in the lungs. In mice, obesity augments the airway hyperresponsiveness and neutrophil recruitment induced by acute ozone exposure. Therefore, we examined the role of IL-17A in obesity-related increases in the response to ozone observed in obese mice. Lean wild-type and obese db/db mice were pretreated with IL-17A-blocking or isotype antibodies, exposed to air or ozone (2 ppm for 3 h), and evaluated 24 hours later. Microarray analysis of lung tissue gene expression was used to examine the mechanistic basis for effects of anti-IL-17A. Compared with lean mice, ozone-exposed obese mice had greater concentrations of BAL IL-17A and greater numbers of pulmonary IL-17A+ cells. Ozone-induced increases in BAL IL-23 and CCL20, cytokines important for IL-17A+ cell recruitment and activation, were also greater in obese mice. Anti-IL-17A treatment reduced ozone-induced airway hyperresponsiveness toward levels observed in lean mice. Anti-IL-17A treatment also reduced BAL neutrophils in both lean and obese mice, possibly because of reductions in CXCL1. Microarray analysis identified gastrin-releasing peptide (GRP) receptor (Grpr) among those genes that were both elevated in the lungs of obese mice after ozone exposure and reduced after anti-IL-17A treatment. Furthermore, ozone exposure increased BAL GRP to a greater extent in obese than in lean mice, and GRP-neutralizing antibody treatment reduced obesity-related increases in ozone-induced airway hyperresponsiveness and neutrophil recruitment. Our data indicate that IL-17A contributes to augmented responses to ozone in db/db mice. Furthermore, IL-17A appears to act at least in part by inducing expression of Grpr.

Full Text

Duke Authors

Cited Authors

  • Mathews, JA; Krishnamoorthy, N; Kasahara, DI; Hutchinson, J; Cho, Y; Brand, JD; Williams, AS; Wurmbrand, AP; Ribeiro, L; Cuttitta, F; Sunday, ME; Levy, BD; Shore, SA

Published Date

  • March 2018

Published In

Volume / Issue

  • 58 / 3

Start / End Page

  • 341 - 351

PubMed ID

  • 28957638

Pubmed Central ID

  • 28957638

Electronic International Standard Serial Number (EISSN)

  • 1535-4989

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2017-0071OC

Language

  • eng

Conference Location

  • United States