CC16 Augmentation Reduces Exaggerated COPD-Like Disease in Cc16-Deficient Mice

Authors

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
Zhang Li
Haider Khamas
Bartolome Celli
Aprile L Pilon
Francesca Polverino
Caroline A Owen

Language

English

Publication Date

3-22-2023

Journal

JCI Insight

DOI

10.1172/jci.insight.130771

PMID

36787195

PMCID

PMC10070105

PubMedCentral® Posted Date

3-22-2023

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Animals, Humans, Mice, Lung, NF-kappa B, Pneumonia, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Nicotiana, Immunology, Inflammation, Innate immunity, NF-kappaB

Published Open-Access

yes

Recommended Citation

Rojas-Quintero, Joselyn; Laucho-Contreras, Maria Eugenia; Wang, Xiaoyun; et al., "CC16 Augmentation Reduces Exaggerated COPD-Like Disease in Cc16-Deficient Mice" (2023). Faculty and Staff Publications. 1804.
https://digitalcommons.library.tmc.edu/baylor_docs/1804