DNA vector augments inflammation in epithelial cells via EGFR-dependent regulation of TLR4 and TLR2

Abstract

Gene delivery applications to treat lung diseases are, in some instances, suboptimal due to deleterious host inflammatory reactions. Current DNA plasmids (pDNA) exert toxicity in part via unmethylated CpG motifs that stimulate Toll-like receptor (TLR)9-expressing leukocytes; however, the airway epithelial response has not been well defined. Bronchial epithelial cells (BEAS-2B) were exposed to pDNA complexes and inflammatory mediators were measured. As patients with inflammatory lung disease are susceptible to infectious exacerbations, we also evaluated the reciprocal inflammatory response to pDNA and bacterial components lipopolysaccharide (LPS) and lipoteichoic acid (LTA), recognized by TLR..