Interleukin-17A Deficiency Attenuated Emphysema and Bone Loss in Mice Exposed to Cigarette Smoke

Int J Chron Obstruct Pulmon Dis. 2020 Feb 10:15:301-310. doi: 10.2147/COPD.S235384. eCollection 2020.

Abstract

Background and purpose: Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease, which is associated with various comorbidities including osteoporosis. Interleukin(IL)-17 has been reported to play important roles in the pathogenesis of COPD and also associated with bone destruction in inflammatory diseases. However, the role of IL-17A in COPD-related osteoporosis is yet unknown. The purpose of our study was to investigate the potential contribution of IL-17A in COPD-related bone loss.

Materials and methods: We examined the bone mass and bone microarchitecture in wild-type and IL-17A-/- mice exposed to long-term cigarette smoke (CS). Osteoclast activities and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in bone tissues were assessed, and the blood levels of inflammatory cytokines were measured.

Results: Less bone loss as well as attenuated emphysema were shown in IL-17A-/- mice compared with wild-type mice. CS-exposed IL-17A-/- mice had decreased TRAP+ osteoclast numbers and lower RANKL expression compared with CS-exposed wild-type mice. Inflammatory cytokines including IL-6 and IL-1β in circulation were decreased in IL-17A-/- mice exposed to CS compared with wild-type mice.

Conclusion: This study indicates that IL-17A is involved in CS-induced bone loss and may be a common link between COPD and osteoporosis.

Keywords: chronic obstructive pulmonary disease; interleukin 17; osteoporosis; receptor activator of nuclear factor-κB ligand.

MeSH terms

  • Animals
  • Bone Density
  • Bone Remodeling
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Femur / diagnostic imaging
  • Femur / metabolism*
  • Femur / physiopathology
  • Inflammation Mediators / metabolism
  • Interleukin-17 / deficiency*
  • Interleukin-17 / genetics
  • Lung / metabolism*
  • Lung / pathology
  • Lung / physiopathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoporosis / genetics
  • Osteoporosis / metabolism
  • Osteoporosis / physiopathology
  • Osteoporosis / prevention & control*
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / prevention & control*
  • Pulmonary Emphysema / genetics
  • Pulmonary Emphysema / metabolism
  • Pulmonary Emphysema / physiopathology
  • Pulmonary Emphysema / prevention & control*
  • RANK Ligand / metabolism
  • Smoke / adverse effects*
  • Tobacco Products / adverse effects*

Substances

  • Cytokines
  • Il17a protein, mouse
  • Inflammation Mediators
  • Interleukin-17
  • RANK Ligand
  • Smoke
  • Tnfsf11 protein, mouse