Clostridium perfringens Beta1 toxin induces macrophage pyroptosis and ferroptosis through the purinergic receptor P2X7-Ca2+ axis.
10.12122/j.issn.1673-4254.2025.10.09
- Author:
Siyu ZHANG
1
;
Linwu RAN
2
;
Jin ZENG
1
;
Yujiong WANG
1
Author Information
1. College of Life Sciences, Ningxia University, Yinchuan 750021, China.
2. Laboratory Animal Center, Ningxia Medical University, Yinchuan 750004, China.
- Publication Type:Journal Article
- Keywords:
Clostridium perfringens Beta1 toxin;
P2X7 receptor;
calcium dyshomeostasis;
ferroptosis;
pyroptosis
- MeSH:
Animals;
Pyroptosis/drug effects*;
Receptors, Purinergic P2X7/metabolism*;
Mice;
Mice, Inbred BALB C;
Ferroptosis/drug effects*;
Humans;
Calcium/metabolism*;
Macrophages/drug effects*;
Bacterial Toxins/toxicity*
- From:
Journal of Southern Medical University
2025;45(10):2126-2134
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the toxic mechanism of Clostridium perfringens Beta1 toxin mediated by P2X7 receptor-induced calcium dyshomeostasis.
METHODS:Ten-day-old BALB/c mice were randomly divided into control group, recombinant Beta1 toxin (rCPB1) group, PD151746 group, and PD151746+rCPB1 group, and all the treatment agents were administered by gavage. The changes in expressions of inflammatory factors in the jejunum of the mice were detected using antibody chip technology to explore the regulatory role of calcium dyshomeostasis in Beta1 toxin-induced inflammatory injury level. In the cell experiment, THP-1 cells were transfected with a si-RNA targeting P2X7 receptor and treated with rCPB1, and the changes in cell survival rate, levels of Ca2+, ROS and ATP, and expressions of pyroptosis and ferroptosis markers were determined.
RESULTS:Oral administration of rCPB1 significantly increased the levels of inflammatory cytokines in the jejunal tissue of the neonatal mice, but their levels were significantly decreased after treatment with PD151746. In THP-1 cells, rCPB1 treatment significantly decreased cell survival and increased the levels of Ca2+, ROS, ATP and the expressions of pyroptosis and ferroptosis markers, and these changes were obviously attenuated by P2X7 receptor knockdown.
CONCLUSIONS:P2X7 receptor-mediated functional pore formation by Beta1 toxin can further lead to calcium dyshomeostasis, thereby triggering excessive accumulation of ROS to subsequently induce the co-occurrence of pyroptosis and ferroptosis.
