Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema

Am J Physiol Lung Cell Mol Physiol. 2015 Jul 15;309(2):L188-95. doi: 10.1152/ajplung.00388.2014. Epub 2015 May 29.

Abstract

Smoking is the main risk factor for the development of the chronic obstructive pulmonary disease (COPD) in Western countries. Recent studies suggest that IL-17A and Th17 cells play a role in the pathogenesis of COPD. We used a murine model of chronic cigarette smoke (CS) exposure to explore the contribution of IL-17A to CS-induced lung damage and loss of pulmonary function. Histology and morphometry showed that IL-17A deficiency spontaneously resulted in a loss of lung structure under basal conditions. Even though inflammatory markers [IL-1β and granulocyte colony-stimulating factor (G-CSF)] were decreased in IL-17A-deficient mice (IL-17A(-/-)) exposed to CS compared with wild-type (WT) mice, IL-17A(-/-) mice were per se not protected from CS-induced emphysematous disease. Assessment of pulmonary function showed that IL-17A(-/-) mice were partially protected from CS-induced changes in total lung capacity. However, the respiratory elastance decreased and respiratory compliance increased in IL-17A(-/-) mice after exposure to CS. Morphometry revealed destruction of lung tissue in CS-exposed IL-17A(-/-) mice similar to WT mice. The expression of elastin was decreased in air-exposed IL-17A(-/-) mice and in CS-exposed WT and IL-17A(-/-) mice. Thus, in the present model of sterile CS-exposure, IL-17A contributes to normal lung homeostasis and does not mediate CS-induced loss of lung structure and pulmonary function.

Keywords: IL-17A; cigarette smoke; emphysema; lung damage; pulmonary function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Female
  • Forced Expiratory Volume
  • Homeostasis
  • Interleukin-17 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pneumonia / chemically induced
  • Pneumonia / metabolism
  • Pneumonia / pathology*
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology*
  • Pulmonary Emphysema / chemically induced
  • Pulmonary Emphysema / metabolism
  • Pulmonary Emphysema / pathology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Respiratory Function Tests
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking / adverse effects*

Substances

  • Cytokines
  • Il17a protein, mouse
  • Interleukin-17
  • RNA, Messenger