Delivery of RAGE Binding Peptide for acute lung injury therapy

Abstract

Acute lung injury (ALI) is an umbrella term for inflammatory conditions of the lung due to various causes, such as infection, sepsis, multiple transfusions, and ischemia/reperfusion. The only clinical option for ALI treatment is oxygen supplementation by intratracheal incubation. In this study, a RAGE binding peptide (RBP) was designed, based on the RAGE binding site of high mobility group box-1 (HMGB-1). The recombinant RBP was produced and purified in the bacterial overexpression system. We hypothesized that RBP would bind to RAGE on the surface of the cells and induce endocytosis, resulting in inhibition of the interaction between RAGE and its ligands. To confirm this hypothesis, the down-regulation of RAGE mediated inflammation reaction was evaluated in in vitro and in vivo ALI models. The Raw 264.7-macrophage cells were activated by lipopolysaccharide (LPS) and then, treated with RBP. The results showed that pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interlukin-1β(IL-1β). Intratracheal administration of RBP into the ALI animal models reduced the inflammation reaction, reducing pro-inflammatory cytokines. The results suggest that RBP may be useful to the treatment of inflammatory diseases such as ALI. Keywords: anti-inflammatory, acute lung injury, Receptor for advanced glycation end products(RAGE), recombinant peptide, RAGE Binding Peptide(RBP)