Igf1r deficiency attenuates lung inflammation in a mice model of sub-chronic cigarette smoke exposure

Cigarette smoke (CS) is an important risk factor in chronic inflammatory pulmonary diseases, including COPD. Insulin-like Growth Factor 1 Receptor (IGF1R) is a trans-membrane tyrosine kinase that belongs to the IGF signaling system. IGF activity maintains lung homeostasis and is involved in several pulmonary diseases. In mice, generalized IGF1R deficiency counteracts respiratory inflammation after different respiratory challenges, including bleomycin and allergens (Sci Rep 2017, 7:4290; Allergy 2017, 72:1317). In order to investigate the role of IGF1R in CS-induced lung inflammation, male Igf1r-deficient and control mice received 1 hour CS or normal air exposures twice daily, 6 day per week, over 4 weeks. In addition, Igf1r KO and normal mouse embryonic fibroblasts (MEFs) were treated with cigarette smoke extract (CSE) to explore the effect of IGF1R absence in CSE-mediated cellular and mitochondrial alterations. CS exposure induced inflammation in the lungs of all mice. Infiltration of inflammatory cells in the airway was the most notable effect of CS exposure. Differential cell counting revealed a significant reduction of neutrophil numbers in the bronchoalveolar fluid (BALF) of Igf1r-deficient mice compared to controls. Furthermore, alveolar macrophage size profile was less enriched in large macrophages in the BALF from Igf1r-deficient mice. In MEFs, preliminary results suggest a milder effect of CSE treatment on cellular morphology and the distribution, shape and fragmentation index of mitochondria in Igf1r KO cells. These results suggest that IGF1R could play an important role in CS-mediated lung inflammation and might participate in COPD pathogenesis.