| First Author | Rojas-Quintero J | Year | 2023 |
| Journal | JCI Insight | Volume | 8 |
| Issue | 6 | PubMed ID | 36787195 |
| Mgi Jnum | J:336123 | Mgi Id | MGI:7460713 |
| Doi | 10.1172/jci.insight.130771 | Citation | Rojas-Quintero J, et al. (2023) CC16 augmentation reduces exaggerated COPD-like disease in Cc16-deficient mice. JCI Insight 8(6) |
| abstractText | 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-kappaB activation in their lungs. It is unclear whether CC16 augmentation can reverse exaggerated COPD in CS-exposed Cc16-/- mice and whether increased NF-kappaB 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-kappaB inhibitor versus vehicle beginning at the midpoint of the exposures. COPD-like disease and NF-kappaB 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-kappaB 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-kappaB activation in luciferase reporter A549 cells. Thus, rhCC16 treatment limits COPD progression in CS-exposed Cc16-/- mice partly by inhibiting NF-kappaB activation and represents a potentially novel therapeutic approach for COPD. |
