Club cell protein 16 (Cc16) deficiency increases inflamm-aging in the lungs of mice

Maria E. Laucho-Contreras, Francesca Polverino, Joselyn Rojas-Quintero, Xiaoyun Wang, Caroline A. Owen

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Low serum CC16 levels are associated with accelerated lung function decline in human population studies, but it is not known whether low serum CC16 levels contribute to lung function decline, or are an epiphenomenon. We tested the hypothesis that unchallenged Cc16−/− mice develop accelerated rates of pulmonary function test abnormalities and pulmonary pathologies over time compared with unchallenged WT mice. Respiratory mechanics, airspace enlargement, and small airway fibrosis were measured in unchallenged wild-type (WT) versus Cc16−/− mice over 6–18 months of age. Lung leukocyte counts and lung levels of metalloproteinases (Mmps), cytokines, oxidative stress, cellular senescence markers (p19 and p21), and lung cell apoptosis, and serum C-reactive protein (CRP) levels were measured in age-matched WT versus Cc16−/− mice. Unchallenged Cc16−/− mice developed greater increases in lung compliance, airspace enlargement, and small airway fibrosis than age-matched WT mice over 6–18 months of age. Cc16−/− mice had greater: (1) lung leukocyte counts; (2) lung levels of Ccl2, Ccl-5, interleukin-10, Mmp-2, and Mmp-9; (3) pulmonary oxidative stress levels, (4) alveolar septal cell apoptosis and staining for p16 and p21; and (5) serum CRP levels. Unchallenged Cc16−/− mice had greater nuclear factor-κB (NF-κB) activation in their lungs than age-matched WT mice, but similar lung levels of secretory phospholipase-A2 activity. Cc16 deficiency in mice leads spontaneously to an accelerated lung aging phenotype with exaggerated pulmonary inflammation and COPD-like lung pathologies associated with increased activation of NF- κB in the lung. CC16 augmentation strategies may reduce lung aging in CC16-deficient individuals.

Original languageEnglish (US)
Article numbere13797
JournalPhysiological reports
Volume6
Issue number15
DOIs
StatePublished - Aug 2018
Externally publishedYes

Keywords

  • Club cell protein-16
  • emphysema
  • inflammation
  • nuclear factor-κB
  • small airway fibrosis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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