Characterization of the acute inflammatory profile and resolution of airway inflammation after Igf1r-gene targeting in a murine model of HDM-induced asthma

PLoS One. 2017 Dec 22;12(12):e0190159. doi: 10.1371/journal.pone.0190159. eCollection 2017.

Abstract

Asthma is a chronic inflammatory disease characterized by bronchial hyperresponsiveness, mucus overproduction and airway remodeling. Notably, we have recently demonstrated that insulin-like growth factor 1 receptor (IGF1R) deficiency in mice attenuates airway hyperresponsiveness and mucus secretion after chronic house dust mite (HDM) exposure. On this basis, inbred C57BL/6 and Igf1r-deficient mice were given HDM extract to study the acute inflammatory profile and implication of Igf1r in acute asthma pathobiology. Additionally, Igf1r-deficiency was therapeutically induced in mice to evaluate the resolution of HDM-induced inflammation. Acute HDM exposure in inbred C57BL/6 mice led to a progressive increase in inflammation, airway remodeling and associated molecular indicators. Preventively-induced Igf1r-deficiency showed reduced neutrophil and eosinophil numbers in BALF and bone marrow, a significant reduction of airway remodeling and decreased levels of related markers. In addition, therapeutic targeting of Igf1r promoted the resolution of HDM-induced-inflammation. Our results demonstrate for the first time that Igf1r is important in acute asthma pathobiology and resolution of HDM-induced inflammation. Thus, IGF1R is suggested to be a promising candidate for future therapeutic approaches for the treatment and prevention of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Asthma / therapy*
  • Bone Marrow Cells
  • Bronchoalveolar Lavage Fluid
  • Disease Models, Animal*
  • Gene Targeting*
  • Inflammation / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Receptor, IGF Type 1 / genetics*

Substances

  • Receptor, IGF Type 1

Grants and funding

This work was supported by grants from the Fundación Rioja Salud (Gobierno de La Rioja, Spain), ERDF (European Regional Development Fund) and the ESF (European Social Fund) to JGP; and the Swedish Heart-Lung Foundation (20150525, 20130636), the Konsul Th C Berghs research foundation, the Karolinska Institutet, and the Centre for Allergy Research at Karolinska Institutet to MA.