Combination therapy of HO-1 gene and Lipopolysaccharide binding peptide from HMGB1A in animal model of LPS-induced acute lung injury.

Abstract

Acute lung injury (ALI) is an inflammatory disease caused by lung infection, sepsis, trauma, aspiration, or ischemia. In this study, the combinational therapy with heme oxygenase-1 (HO-1) gene and lipopolysaccharide (LPS)-binding peptide (LBP) regions from high mobility group box-1 box A (HMGB1A) was evaluated for the treatment of ALI. As a gene carrier, deoxycholic acid was conjugated to low molecular weight polyethylenimine (PEI, 1.8 kDa). Deoxycholic acid conjugated PEI (DA-3) was characterized as a carrier of the HO-1 gene in vitro. Gel retardation and heparin competition assays showed that DA-3 formed stable complex with DNA by electrostatic interaction. In the transfection and luciferase assay, DA-3 had higher transfection efficiency than high molecular weight PEI (PEI25k, 25kDa) and Lipofectamine in the L2 lung epithelial cells. These results were confirmed by the transfection assays with the HO-1 gene. In cytokine assays, the combined treatment with the HO-1 gene and LBP reduced the pro-inflammatory cytokines more efficiently that the single treatment of the HO-1 gene or LBP in the LPS activated macrophage cells. Therefore, the HO-1 gene and LBP may be useful for combination therapy for ALI.