Intestinal guard: Human CXCL17 modulates protective response against mycotoxins and CXCL17-mimetic peptides development

Biochem Pharmacol. 2021 Jun:188:114586. doi: 10.1016/j.bcp.2021.114586. Epub 2021 Apr 29.

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.

Keywords: Apoptosis; CXCL17; Inflammation; Mimetic peptides; Mycotoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / pharmacology*
  • Caco-2 Cells
  • Chemokines, CXC / biosynthesis*
  • Chemokines, CXC / chemical synthesis
  • Chemokines, CXC / genetics
  • Dose-Response Relationship, Drug
  • Drug Development / methods*
  • Humans
  • Mycotoxins / toxicity*
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism

Substances

  • CXCL17 protein, human
  • Chemokines, CXC
  • Mycotoxins
  • Peptide Fragments
  • Reactive Oxygen Species