CC16 augmentation reduces exaggerated COPD-like disease in Cc16-deficient mice

Joselyn Rojas-Quintero, Maria Eugenia Laucho-Contreras, Xiaoyun Wang, Quynh Anh Fucci, Patrick R. Burkett, Se Jin Kim, Duo Zhang, Yohannes Tesfaigzi, Yuhong Li, Abhiram R. Bhashyam, Li Zhang, Haider Khamas, Bartolome Celli, Aprile L. Pilon, Francesca Polverino, Caroline A. Owen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Low Club Cell 16 kDa protein (CC16) plasma levels are linked to accelerated lung function decline in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke-exposed (CS-exposed) Cc16-/- mice have exaggerated COPD-like disease associated with increased NF-κB activation in their lungs. It is unclear whether CC16 augmentation can reverse exaggerated COPD in CS-exposed Cc16-/- mice and whether increased NF-κB activation contributes to the exaggerated COPD in CS-exposed Cc16-/- lungs. CS-exposed WT and Cc16-/- mice were treated with recombinant human CC16 (rhCC16) or an NF-κB inhibitor versus vehicle beginning at the midpoint of the exposures. COPD-like disease and NF-κB activation were measured in the lungs. RhCC16 limited the progression of emphysema, small airway fibrosis, and chronic bronchitis-like disease in WT and Cc16-/- mice partly by reducing pulmonary inflammation (reducing myeloid leukocytes and/or increasing regulatory T and/or B cells) and alveolar septal cell apoptosis, reducing NF-κB activation in CS-exposed Cc16-/- lungs, and rescuing the reduced Foxj1 expression in CS-exposed Cc16-/- lungs. IMD0354 treatment reduced exaggerated lung inflammation and rescued the reduced Foxj1 expression in CS-exposed Cc16-/- mice. RhCC16 treatment reduced NF-κB activation in luciferase reporter A549 cells. Thus, rhCC16 treatment limits COPD progression in CS-exposed Cc16-/- mice partly by inhibiting NF-κB activation and represents a potentially novel therapeutic approach for COPD.

Original languageEnglish (US)
Article numbere130771
JournalJCI Insight
Volume8
Issue number6
DOIs
StatePublished - Mar 22 2023
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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