Intestinal guard: Human CXCL17 modulates protective response against mycotoxins and CXCL17-mimetic peptides
Chongjun Sun1, Haokun Shen1, Haiming Cai1
1Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
Abstract:
Mycotoxin contamination is an ongoing and growing issue that can create health risks and even cause death. Unfortunately, there is currently a lack of specific therapy against mycotoxins with few side effects. On the other hand, the strategic expression of CXCL17 in mucosal tissues suggests that it may be involved in immune response when exposed to mycotoxins, but the exact role of CXCL17 remains largely unknown. Using Caco-2 as a cell model of the intestinal epithelial barrier (the first line of defense against mycotoxins), we showed that a strong production of ROS-dependent CXCL17 was triggered by mycotoxins via p38 and JNK pathways. Under the mycotoxins stress, CXCL17 modulated enhanced immuno-protective response with a remission of inflammation and apoptosis through PI3K/AKT/mTOR. Based on our observed feedback of CXCL17 to the mycotoxins, we developed the CXCL17-mimetic peptides in silico (CX1 and CX2) that possessed the safety and the capability to ameliorate mycotoxins-inducible inflammation and apoptosis. In this study, the identification of detoxifying feature of CXCL17 is a prominent addition to the chemokine field, pointing out a new direction for curing the mycotoxins-caused damage.
Insights
Mycotoxins trigger CXCL17 production in the gut, which helps reduce inflammation and cell death. This discovery led to the development of CXCL17-mimetic peptides for potential mycotoxin damage treatment.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- Mycotoxin contamination poses significant health risks due to a lack of targeted therapies.
- The chemokine CXCL17's role in mucosal immune responses to mycotoxins is largely unexplored.
Purpose of the Study:
- To investigate the role of CXCL17 in the intestinal epithelial response to mycotoxins.
- To explore the potential of CXCL17-mimetic peptides as a therapeutic strategy against mycotoxin-induced damage.
Main Methods:
- Utilized Caco-2 cells as a model for the intestinal epithelial barrier.
- Investigated mycotoxin-induced CXCL17 production via p38 and JNK pathways, involving ROS.
- Analyzed the anti-inflammatory and anti-apoptotic effects of CXCL17 through the PI3K/AKT/mTOR pathway.
- Developed and assessed CXCL17-mimetic peptides (CX1 and CX2) in silico.
Main Results:
- Mycotoxins induced ROS-dependent CXCL17 production in Caco-2 cells through p38 and JNK signaling.
- CXCL17 mitigated mycotoxin-induced inflammation and apoptosis via the PI3K/AKT/mTOR pathway.
- In silico developed CXCL17-mimetic peptides (CX1 and CX2) demonstrated potential for ameliorating mycotoxin effects.
Conclusions:
- CXCL17 possesses a detoxifying feature against mycotoxins, representing a novel addition to chemokine research.
- CXCL17-mimetic peptides offer a promising new therapeutic direction for managing mycotoxin-induced damage.
