Therapeutic Effect of Fish Oil on Acute Lung Injury through GPR120 Activation and Club Cell Proliferation

Abstract

Background In clinical setting, fish oil administration to ICU patients with acute lung injury has been investigated to shorten hospital stay. Recently, a G protein-coupled receptor, FFA4 (aka GPR120) has been elucidated as an omega-3 fatty acid-sensing receptor. METHODS: FFA4 deficient and wild type male Balb/c mouse were used. Mice of 8 weeks received one intraperitoneal injection of 30 mg/kg of naphthalene. RESULTS: Acute lung injury was induced by intraperitoneal injection of 30 mg/kg nathphalene. Bronchiolar epithelial cells were destroyed in a day. Appearance of bronchiolar epithelial cells after destruction was observed from 21 days after naphthalene injection. However, in omega-3 supplemented mice the recovery was accelerated more than 14 days. FFA4 expression was confirmed in CC-10 positive Club cells isolated from wild type Balb/c mice and deficiency of the expression in the Club cells from FFA4 deficient mice by immunohistochemistry. Isolated Club cells were proliferated by docosahexaenoic acid. Also in FFA4-deficient Club cells proliferation-stimulatory effect was absent. Furthermore, treatment of docosahexaenoic acid inhibited expression of goblet cell marker, Muc-5A and type epithelial cell marker, pro SP-C. SUMMARY: We found fish oil shorten the recovery of bronchiolar epithelial cells after naphthalene-induced lung injury in vivo. We also found proliferation-stimulatory and differentiation-inhibitory effects of docosahexaenoic acid in Club cells via FFA4. This finding would be a basic knowledge for applying fish oil supplement to ICU patients with acute lung injury or acute respiratory distress syndrome (ARDS).