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

Autor:	Rojas-Quintero J; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Laucho-Contreras ME; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Fundación Neumológica Colombiana, Bogotá, Colombia., Wang X; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Clinical and Experimental Therapeutics program, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, USA., Fucci QA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Burkett PR; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Kim SJ; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Zhang D; Clinical and Experimental Therapeutics program, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, USA.; Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA., Tesfaigzi Y; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Li Y; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Bhashyam AR; Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA., Li Z; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Khamas H; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Celli B; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Pilon AL; APCBio Innovations, Inc., Rockville, Maryland, USA., Polverino F; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Owen CA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2023 Mar 22; Vol. 8 (6). Date of Electronic Publication: 2023 Mar 22.
DOI:	10.1172/jci.insight.130771
Abstrakt:	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.
Databáze:	MEDLINE
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