Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD)

Expert Opin Ther Targets. 2016 Jul;20(7):869-83. doi: 10.1517/14728222.2016.1139084. Epub 2016 Feb 11.


Introduction: Club cell protein 16 (CC16) is the most abundant protein in bronchoalveolar lavage fluid. CC16 has anti-inflammatory properties in smoke-exposed lungs, and chronic obstructive pulmonary disease (COPD) is associated with CC16 deficiency. Herein, we explored whether CC16 is a therapeutic target for COPD.

Areas covered: We reviewed the literature on the factors that regulate airway CC16 expression, its biologic functions and its protective activities in smoke-exposed lungs using PUBMED searches. We generated hypotheses on the mechanisms by which CC16 limits COPD development, and discuss its potential as a new therapeutic approach for COPD.

Expert opinion: CC16 plasma and lung levels are reduced in smokers without airflow obstruction and COPD patients. In COPD patients, airway CC16 expression is inversely correlated with severity of airflow obstruction. CC16 deficiency increases smoke-induced lung pathologies in mice by its effects on epithelial cells, leukocytes, and fibroblasts. Experimental augmentation of CC16 levels using recombinant CC16 in cell culture systems, plasmid and adenoviral-mediated over-expression of CC16 in epithelial cells or smoke-exposed murine airways reduces inflammation and cellular injury. Additional studies are necessary to assess the efficacy of therapies aimed at restoring airway CC16 levels as a new disease-modifying therapy for COPD patients.

Keywords: Bronchoalveolar lavage fluid; CC10; CC16; COPD; Club cells; chronic bronchitis; emphysema; formyl peptide receptor-2; lipoxin A4; lung inflammation; nuclear factor kappa B; phospholipase A2; recombinant therapy; secretoglobin 1A1; serum amyloid A; small airway remodeling; toll-like receptor; uteroglobin.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Bronchoalveolar Lavage Fluid
  • Drug Design
  • Epithelial Cells / metabolism
  • Humans
  • Mice
  • Molecular Targeted Therapy*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Severity of Illness Index
  • Smoking / adverse effects
  • Uteroglobin / administration & dosage*
  • Uteroglobin / metabolism


  • Anti-Inflammatory Agents
  • SCGB1A1 protein, human
  • Uteroglobin