Protecting intestinal epithelial cells against deoxynivalenol and E. coli damage by recombinant porcine IL-22

Abstract

Pigs suffer enteritis induced by pathogenic bacteria infection and toxins in the moldy feed, which cause intestinal epithelial damage and diarrhea through the whole breeding cycle. Interleukin-22 (IL-22) plays a critical role in maintaining intestinal mucosal barrier function through repairing intestinal epithelial damage. However, little was known about the effects of IL-22 against apoptosis caused by toxins and infection of intestinal pathogens in the intestinal epithelium, especially in pigs. In this study, we had successfully used prokaryotic expression system to produce recombinant porcine interleukin-22. Meanwhile, purified rIL-22 could activate STAT3 signal pathway and have been demonstrated to be safe to IPEC-J2 cells by increasing E-cadherin expression, without proinflammatory cytokines changes. Furthermore, rIL-22 reversed apoptosis induced by deoxynivalenol (DON) and played a vital part in repairing the intestinal injury. We also found that rIL-22 stimulated epithelial cells to secrete pBD-1 against enterotoxigenic E. coli (ETEC) K88 infection, as well as alleviating apoptosis ratio. This study provided a theoretical basis for curing intestinal inflammation caused by ETEC infection and epithelial apoptosis induced by DON with rIL-22 in pigs.

A Double Edged Sword Role of Interleukin-22 in Wound Healing and Tissue Regeneration

“…When present at mucosal surfaces, RegIII proteins serve to exhibit antimicrobial action against gram-positive bacteria by binding to the peptidoglycan moieties of bacteria and induce damage to the bacterial cell wall and separate microbiota from intestinal epithelial cells to maintain a symbiotic host-bacterial relationship (79,80). Similarly, recombinant porcine IL-22 activates STAT3 signaling to protect against Escherichia coli infection (81).…”

“…In absence of IL-22, murine model developed liver necrosis upon Salmonella infection (88). In case of chronic Salmonella gastroenteritis model, antibody mediated IL-22 neutralization disrupted the epithelial barrier of intestine and increased the production of pro-inflammatory cytokines in porcine intestinal epithelial cells (81). IL-22 mediated anti-bacterial activity against Salmonella is carried out by phagolysosomal fusion in intestinal epithelial cells (89).…”

Functional Characterization of Porcine NK-Lysin: A Novel Immunomodulator That Regulates Intestinal Inflammatory Response

“…In order to further understand the mechanism of PNKL regulating intestinal barrier function, we explored the expression level of some critical molecules involved in inflammatory response and apoptosis regulation. Enteropathogenic bacteria (ETEC) adhere to the intestinal epithelium and cause severe diarrhea and intestinal inflammation through lipopolysaccharide (LPS), the main component of the cell wall [ 55 ]. LPS cannot directly destroy the integrity of cell structure and activate the signal pathway of apoptosis, but it can bind to TLR4, activate NF-κB, signal pathway, and produce the inflammatory factor (i.e., TNF-α) [ 56 ].…”

Expression and Functional Characterization of a Novel Antimicrobial Peptide: Human Beta-Defensin 118

“…For instance, human β -defensin 1, β -defensin 2, and β -defensin 3 were found to have both the anti-inflammatory and immunoregulatory functions [ 39 – 42 ]. Enterotoxigenic Escherichia coli (ETEC) adheres to the intestinal epithelium and induces severe diarrhea and intestinal inflammation [ 43 ]. In this study, we found that DEFB118 can inhibit the adhesion of E. coli K88 to intestinal epithelial cells.…”