Pulmonary hepcidin protects against acute lung injury (P3345)

Abstract

Abstract Hepcidin is a small cysteine-rich cationic peptide mainly produced by the liver, and is a principle iron regulatory hormone. Hepcidin could modulate acute inflammatory response via interaction with its receptor ferroportin. Recent studies showed that hepcidin was also expressed in tracheal epithelial cells. However, the role of this epithelia-derived hepcidin in lung inflammation remained unknown. Adenovirus-mediated hepcidin specific shRNA and a relative negative control were constructed and were administrated to mice intratracheally. Ten days later, the mice were subjected to cecal ligation and puncture to induce acute lung injury (ALI). The severity of lung injury was scored 24 hours after onset of ALI. The bacterial colony counts, white blood cell counts and total protein content in bronchoalveolar lavage fluid were also measured. Furthermore, the protein levels of ferroportin were analyzed using immunobloting. Adenovirus-mediated hepcidin specific shRNA significantly suppressed tracheal hepcidin levels ten days after administration. Interference of this epithelia-derived hepcidin increased bacterial proliferation, white blood cell counts and total protein content in bronchoalveolar lavage fluid, and thus exacerbated lung injury. However, the ferroportin levels were comparable between the two groups. Tracheal epithelia-derived hepcidin plays an important role in protecting against acute lung injury, which might function via a ferroportin-independent mechanism.