Short peptide 803sp inhibits the inflammatory response induced by Escherichia coli accompanied by M2 polarization of macrophages.

INTRODUCTION: Prolonged antibiotic use has led to increased bacterial resistance, making antibacterial peptides a promising alternative. We previously identified that the anti-apoptotic lncRNA-803 could encode short peptides, though their functions were unknown. METHODS: In this study, we explored the novel peptide 803sp, derived from lncRNA-803, to understand its anti-inflammatory and bactericidal roles. We assessed its antibacterial properties, morphology, efficacy, and safety. Using an Escherichia coli (E. coli)-infected skin wound model, we evaluated histopathological changes, collagen deposition, and tissue remodeling, along with macrophage polarization markers and inflammatory cytokines. RESULTS: Our results show that 803sp is highly effective against E. coli, is blood-compatible, and aids wound healing by reducing inflammation and hematoma, while promoting collagen and blood vessel formation. The application of 803sp is associated with the polarization of macrophages towards the M2 phenotype, characterized by increased CD206 expression and decreased CD80 expression. Consequently, a substantial population of M2 macrophages secretes elevated levels of the anti-inflammatory IL-10, whereas a smaller population of M1 macrophages secretes pro-inflammatory IL-6 and TNF-α. DISCUSSION: Ultimately, 803sp enhances wound healing after E. coli infection through both bactericidal and anti-inflammatory pathways. The new antibacterial peptide 803sp effectively inhibits the growth of E. coli, making it a promising alternative to traditional antibiotics.