Molecular characterization and function of JAK/STAT pathway in IPEC-J2 cells during Clostridium perfringens beta2 toxin stimulation

Vet Res Commun. 2023 Sep;47(3):1177-1184. doi: 10.1007/s11259-023-10118-w. Epub 2023 Jul 12.

Abstract

Intestinal infection with C. perfringens is responsible for outbreaks of diarrhea in piglets. Janus kinase / signal transducer and activator of transcription (JAK/STAT) is a vital signaling pathway that regulates cellular activity and inflammatory response, closely correlated with multiple diseases development and advances. Currently, the potential effect of JAK/STAT on C. perfringens beta2 (CPB2) treatment on porcine intestinal epithelial (IPEC-J2) cells has not been explored. The expression of JAK/STAT genes or proteins in IPEC-J2 cells induced by CPB2 were observed by qRT-PCR and Western blot, and further used WP1066 to explore the effect of JAK2/STAT3 on mechanism employed by CPB2 on apoptosis, cytotoxicity, oxidative stress and inflammatory cytokines of IPEC-J2 cells. JAK2, JAK3, STAT1, STAT3, STAT5A and STAT6 were highly expressed in CPB2-induced IPEC-J2 cells, among which STAT3 had the highest expression. Moreover, apoptosis, cytotoxicity and oxidative stress were attenuated via blocking the activation of JAK2/STAT3 by using WP1066 in CPB2-treated IPEC-J2 cells. Furthermore, WP1066 significantly suppressed the secretion of interleukin (IL)-6, IL-1β and TNF-α induced by CPB2 in IPEC-J2 cells.Our findings provide some insights into the functional roles of JAK2/STAT3 in piglets against to C. perfringens infection.

Keywords: Apoptosis; C. perfringens beta2; Inflammatory response; JAK2/STAT3 pathway; Pig.

MeSH terms

  • Animals
  • Bacterial Toxins / toxicity
  • Blotting, Western
  • Cell Line
  • Clostridium Infections* / metabolism
  • Clostridium Infections* / pathology
  • Clostridium Infections* / veterinary
  • Clostridium perfringens* / physiology
  • Gene Expression Profiling
  • Intestines / cytology
  • Intestines / metabolism
  • Janus Kinases / metabolism
  • Pyridines / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction* / drug effects
  • Swine
  • Swine Diseases* / metabolism
  • Swine Diseases* / pathology
  • Tyrphostins / pharmacology

Substances

  • Janus Kinases
  • WP1066
  • Pyridines
  • Tyrphostins
  • cpb2 protein, Clostridium perfringens
  • Bacterial Toxins