Role of myeloid cell CYP19A1 in lung airway tissue repair following naphthalene induced epithelial injury in a mouse model

CYP19A1 (the aromatase) is a key enzyme in the biosynthesis of estrogens, which have important regulatory functions, including roles as a major mitogenic stimulus for cellular proliferation. In this study, we are testing the hypothesis that macrophage CYP19A1 can increase estrogen production and/or regulate the function of macrophages at sites of tissue injury, thereby influencing the balance between normal tissue repair and pathogenic outcomes related to abnormal epithelial repair. A myeloid cell (including macrophage) specific Cyp19a1 ‐null mouse model was generated and characterized. Wild‐type and Cyp19a1‐null mice were treated with naphthalene (200 mg/kg, IP) to induce acute lung injury, or with corn oil as a vehicle control. Mouse lung was examined at 24 hour, 72 hours, or 14 days after the treatment, for extent of acute airway injury, post‐injury cellular proliferation, and tissue repair, respectively. At 24 hours, a genotype difference in the extent of naphthalene‐induced airway injury was not detected. At 72 hours, the fraction of airway epithelial cells that are positive for the cell proliferation marker Ki67 was higher in naphthalene‐treated wild‐type mice (40%–70%) than in naphthalene‐treated Cyp19a1‐null mice (20–30%); whereas the fraction was much lower in corn oil treated control mice (3–5%). At 14 days, the bronchiolar epithelium was completely recovered in wild‐type mice, but only partially (<30%) in the Cyp19a1‐null mice, as indicated by the abundance of Club cells (positive for Clara cell secretary protein) in the airway epithelium. Thus, the loss of macrophage CYP19A1 did not impact the degree of naphthalene‐induced lung injury; but it impeded the post‐injury cellular proliferation and tissue repair in the airways. Support or Funding Information Supported in part by NIH grant ES020867