Antibacterial peptide Reg4 ameliorates -induced pulmonary inflammation and fibrosis.

() is a Gram-negative facultative anaerobe that has become an important cause of severe infections in humans, particularly in patients with cystic fibrosis. The development of efficacious methods or mendicants against is still needed. We previously reported that regenerating islet-derived family member 4 (Reg4) has bactericidal activity against Typhimurium, a Gram-negative flagellated bacterium. We herein explore whether Reg4 has bactericidal activity against . In the PAO1-chronic infection model, Reg4 significantly inhibits the colonization of PAO1 in the lung and subsequently ameliorates pulmonary inflammation and fibrosis. Reg4 recombinant protein suppresses the growth motility and biofilm formation capability of PAO1 . Mechanistically, Reg4 not only exerts bactericidal action via direct binding to the cell wall but also enhances the phagocytosis of alveolar macrophages in the host. Taken together, our study demonstrates that Reg4 may provide protection against -induced pulmonary inflammation and fibrosis via its antibacterial activity.IMPORTANCEChronic lung infection with is a leading cause of morbidity and mortality in patients with cystic fibrosis. Due to the antibiotic resistance of , antimicrobial peptides appear to be a potential alternative to combat its infection. In this study, we report an antimicrobial peptide, regenerating islet-derived 4 (Reg4), that showed killing activity against clinical strains of PAO1 and ameliorated PAO1-induced pulmonary inflammation and fibrosis. Experimental data also showed Reg4 directly bound to the bacterial cell membrane and enhanced the phagocytosis of host alveolar macrophages. Our presented study will be a helpful resource in searching for novel antimicrobial peptides that could have the potential to replace conventional antibiotics.