Porcine Beta-Defensin 2 Provides Protection Against Bacterial Infection by a Direct Bactericidal Activity and Alleviates Inflammation via Interference With the TLR4/NF-κB Pathway.

摘要: Porcine beta-defensin 2 (PBD-2) which is a member of the family antimicrobial peptides, widely expressed in pig organs with broad spectrum bactericidal activities confirmed vitro. We previously demonstrated that transgenic (TG) pigs overexpressing PBD-2 could resist infection by porcine pathogen Actinobacillus pleuropneumoniae. In this study, roles protecting against bacterial were further investigated. The biochemical indexes blood sample, body weights, histological morphologies, and weights TG mice expressing measured. Results these showed normal physiological features. An assay Salmonella Typhimurium was conducted on wild-type (WT) mice. possessed higher survival rate, less weight loss, pathological changes smaller recovery rates bacteria after S. Typhimurium. vitro synthetic serum tissue homogenates from displayed direct activity. Moreover, inhibit release proinflammatory cytokines, including IL-6, TNF-α, IL-1β, IL-12, infected or treated lipopolysaccharide (LPS). WT LPS reduced levels cytokines. mouse macrophage cell line RAW 264.7 constructed to detect signal pathways affected PBD-2. suppressing effect cytokines using either supplemented promoter activity mRNA level NF-κB detected, shown significantly activation pathway induced LPS. interaction TLR4 revealed isothermal titration calorimetry far-Western blot coimmunoprecipitation cells. This indicates one reason for interference activation. Overall, study protected through alleviated inflammation interfering TLR4/NF-κB pathway.