Regulation of the Intestinal Barrier Function by Host Defense Peptides

Abstract

Intestinal barrier function is achieved primarily through regulating the synthesis of mucins and tight junction (TJ) proteins, which are critical for maintaining optimal gut health and animal performance. An aberrant expression of TJ proteins results in increased paracellular permeability, leading to intestinal and systemic disorders. As an essential component of innate immunity, host defense peptides (HDPs) play a critical role in mucosal defense. Besides broad-spectrum antimicrobial activities, HDPs promotes inflammation resolution, endotoxin neutralization, wound healing, and the development of adaptive immune response. Accumulating evidence has also indicated an emerging role of HDPs in barrier function and intestinal homeostasis. HDP deficiency in the intestinal tract is associated with barrier dysfunction and dysbiosis. Several HDPs were recently shown to enhance mucosal barrier function by directly inducing the expression of multiple mucins and TJ proteins. Consistently, dietary supplementation of HDPs often leads to an improvement in intestinal morphology, production performance, and feed efficiency in livestock animals. This review summarizes current advances on the regulation of epithelial integrity and homeostasis by HDPs. Major signaling pathways mediating HDP-induced mucin and TJ protein synthesis are also discussed. As an alternative strategy to antibiotics, supplementation of exogenous HDPs or modulation of endogenous HDP synthesis may have potential to improve intestinal barrier function and animal health and productivity.

Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia

“…It is plausible that entinostat, through HDAC inhibition, can reverse V. cholerae-induced disruption of intestinal tight junctions and consequently decrease gut permeability. On the other hand, recent studies have reported that host defense peptides play roles in intestinal barrier function by directly regulating mucin and tight-junction protein expression (37). Cathelicidin-BF, a peptide purified from the venom of the Bungarus fasciatus snake, has been shown to ameliorate lipopolysaccharide (LPS)-induced disruption of the epithelial barrier in rats via prevention of the downregulation of tight-junction proteins (38).…”

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

“…AMPs have a defensive role, but their function cannot be distinguished from those of nutrient acquisition. For example, it has been shown that feeding AMPs to livestock improves nutrient digestibility, intestinal morphology and growth performance [122]. Ultimately, as has been noted elsewhere [33], activities of immune detection and response resemble nutrient breakdown, uptake, and transport, and as the examples above suggest, immune pathways in Drosophila appear to be regulating multiple aspects of host metabolism.…”

Antimicrobial and antiviral effects of human defensins: pathogenetic value and prospective application to medicinal therapy

“…Благодаря многочисленным исследованиям у дефенсинов выявлен широкий диапазон эффектов в регули-ровании иммунитета человека (рис. 2) [14,94,171,245].…”

“…Иммунозащитные пептиды, синтезируясь в клетках кожи в местах потен-циального проникновения микробов, обеспечивают растворимый барьер, который действует как прегра-да для инфекций [39,40]. Если кожа не повреждена, то рост бактерий контролируется бактериостатиче-скими и бактерицидными соединениями, такими как псориазин и РНКаза 7 [171]. Однако при поврежде-нии или инфицировании кожи экспрессия иммуно-защитных пептидов повышается посредством уве-личения их синтеза кератиноцитами и секреции при дегрануляции рекрутированных нейтрофилов.…”