nsc-74859 and Diarrhea

Interleukin-22 (IL-22), a member of the IL-10 superfamily, plays essential roles in fighting against mucosal microbial infection and maintaining mucosal barrier integrity within the intestine. However, little knowledge exists on the ability of porcine IL-22 (pIL-22) to fight against viral infection in the gut. In this study, we found that recombinant mature pIL-22 (mpIL-22) inhibited the infection of multiple diarrhea viruses, including alpha coronavirus, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine rotavirus (PoRV), in the intestinal porcine epithelial cell line J2 (IPEC-J2) cells. mpIL-22 up-regulated the expression of the antimicrobial peptide beta-defensin (BD-2), cytokine IL-18 and IFN-λ. Furthermore, we found that mpIL-22 induced phosphorylation of STAT3 on Ser727 and Tyr705 in IPEC-J2 cells. Inhibition of STAT3 phosphorylation by S3I-201 abrogated the antiviral ability of mpIL-22 and the mpIL-22-induced expression of BD-2, IL-18, and IFN-λ. Together, mpIL-22 inhibited the infection of PoRV and enteric coronaviruses, and up-regulated the expression of antimicrobial genes in IPEC-J2, which were mediated by the activation of the STAT3 signal pathway. The significant antiviral activity of IL-22 to curtail multiple enteric diarrhea viruses in vitro suggests that pIL-22 could be a novel therapeutic against devastating viral diarrhea in piglets.

Topics: Amino Acid Sequence; Aminosalicylic Acids; Animals; Benzenesulfonates; beta-Defensins; Cell Line; Chlorocebus aethiops; Cloning, Molecular; Coronavirus; Coronavirus Infections; Cytokines; Diarrhea; Epithelial Cells; Gene Expression Regulation; Genes, Viral; Interleukin-18; Interleukin-22; Interleukins; Mutation; Phylogeny; Porcine epidemic diarrhea virus; Recombinant Proteins; Rotavirus; Rotavirus Infections; Sequence Alignment; Sequence Homology; Signal Transduction; STAT3 Transcription Factor; Swine; Transmissible gastroenteritis virus; Vero Cells