Intestinal guard: Human CXCL17 modulates protective response against mycotoxins and CXCL17-mimetic peptides development
| Autor: | Haokun Shen, Chongjun Sun, Guanhua Gan, Jinbo Deng, Ding Cao, Zengjue Zhao, Rongxiao He, Linghua Zhang, Junhao Jia, Miaopeng Ma, Pinpin Chu, Min Zeng, Feiping Ming, Zhiyang Chen, Saixiang Feng, Haiming Cai, Jiayi Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
endocrine system Chemokine animal structures p38 mitogen-activated protein kinases Inflammation Biology Biochemistry Protein Structure Secondary 03 medical and health sciences 0302 clinical medicine Immune system Drug Development Biomimetic Materials medicine Humans Amino Acid Sequence Protein kinase B PI3K/AKT/mTOR pathway CXCL17 Pharmacology Dose-Response Relationship Drug technology industry and agriculture food and beverages Mycotoxins Peptide Fragments Protein Structure Tertiary body regions 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Immunology biology.protein medicine.symptom Caco-2 Cells Reactive Oxygen Species Chemokines CXC |
| Zdroj: | Biochemical pharmacology. 188 |
| ISSN: | 1873-2968 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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