Decreased S100A9 expression alleviates Clostridium perfringens beta2 toxin-induced inflammatory injury in IPEC-J2 cells

PeerJ. 2023 Jan 25:11:e14722. doi: 10.7717/peerj.14722. eCollection 2023.

Abstract

Background: S100 calcium-binding protein A9 (S100A9) is a commonly known pro-inflammatory factor involved in various inflammatory responses. Clostridium perfringens (C. perfringens ) type C is known to cause diarrhea in piglets. However, the role of S100A9 in C. perfringens type C-induced infectious diarrhea is unclear.

Methods: Here, the S100A9 gene was overexpressed and knocked down in the IPEC-J2 cells, which were treated with C. perfringens beta2 (CPB2) toxin. The role of S100A9 in CPB2 toxin-induced injury in IPEC-J2 cells was assessed by measuring the levels of inflammatory cytokines, reactive oxygen species (ROS), lactate dehydrogenase (LDH), cell proliferation, and tight junction-related proteins.

Results: The results showed elevated expression of S100A9 in diarrhea-affected piglet tissues, and the elevation of S100A9 expression after CPB2 toxin treatment of IPEC-J2 was time-dependent. In CPB2 toxin-induced IPEC-J2 cells, overexpression of S100A9 had the following effects: the relative expression of inflammatory factors IL-6, IL8, TNF-α, and IL-1β was increased; the ROS levels and LDH viability were significantly increased; cell viability and proliferation were inhibited; the G0/G1 phase cell ratio was significantly increased. Furthermore, overexpression of S100A9 reduced the expression of tight junction proteins in CPB2-induced IPEC-J2 cells. The knockdown of S100A9 had an inverse effect. In conclusion, our results confirmed that S100A9 exacerbated inflammatory injury in CPB2 toxin-induced IPEC-J2 cells, inhibited cell viability and cell proliferation, and disrupted the tight junctions between cells. Thus, decreased S100A9 expression alleviates CPB2 toxin-induced inflammatory injury in IPEC-J2 cells.

Keywords: Clostridium perfringens beta2 toxin; Clostridium perfringens type C; Inflammatory injury; Piglet diarrhea; S100A9 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clostridium perfringens* / genetics
  • Cytokines
  • Diarrhea*
  • Reactive Oxygen Species
  • Swine
  • Tumor Necrosis Factor-alpha

Substances

  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Cytokines

Associated data

  • figshare/10.6084/m9.figshare.21225776.v1

Grants and funding

This work was supported by the Higher Education Innovation Fund of Gansu Province (2022B-106), the National Natural Science Foundation of China (31960646), the Youth Science and Technology Fund Program of Gansu Province (20JR5RA005), and the Protection and Quality Improvement of Gansu Local Pig Germplasm Resources (GSLK-2021-13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.