Resolvin D1 improves bleomycin-induced alveolar maturation arrest in newborn rats

Abstract

Abstract Sustained, non-resolving inflammation is a fundamental mechanism that causes bronchopulmonary dysplasia (BPD). Specialized pro-resolving mediators (SPMs) are attracting attention as the new endogenous anti-inflammatory agents because they facilitate only the resolution phase of inflammation without affecting its acute phase, indispensable for the elimination of noxious microorganisms and damaged tissues. The preventive effects of resolvin D1 (RvD1), an SPM, were analyzed using bleomycin (Bleo)-induced BPD model of neonatal rats. Starting from the postnatal day (PD)-0, Bleo and RvD1 were administered simultaneously. At PD-14, morphological and immunohistochemical analyses, and the expression of key genes suspected to be involved in the Bleo-induced lung damage, were examined. Bleo injection successfully recapitulated the pathological features of BPD, such as alveolar enlargement and simplification with septal thickening. RvD1 effectively inhibited such alveolar dysmorphogenesis with attenuating macrophage infiltration and restoring the arrested capillary growth. It significantly suppressed the Bleo-induced upregulation of insulin-like growth factor-1 (IGF-1), tenascin-C, elastin, and anillin. The changes in IGF-1 protein expression in the bronchial and alveolar epithelia were confirmed by immunostaining. RvD1 effectively improves Bleo-induced model of alveolar maturation arrest of BPD. The supplementation of SPMs including RvD1 seems to be a promising treatment for the infants with BPD.