Research Article: Crotoxin from Crotalus durissus terrificus impairs the establishment of chemically induced colitis in mice associated with formyl peptide receptor signaling
Abstract:
Inflammatory bowel diseases (IBDs) arise from a breakdown in tolerance to intestinal microbiota and are characterized by exacerbated inflammatory responses. Epithelial cells of the gastrointestinal tract play a central role in maintaining barrier integrity and orchestrating immune responses; however, the mechanisms underlying epithelial dysfunction and uncontrolled inflammation remain incompletely understood. Crotoxin (CTX), the main component of Crotalus d. terrificus venom, exhibits immunomodulatory activity, making it a promising tool to investigate epithelial–immune interactions in intestinal inflammation. This study evaluated the effects of CTX on acute colitis induced by trinitrobenzene sulfonic acid (TNBS) in mice, as well as its ability to modulate human epithelial responses. In Caco-2 cells stimulated with IFN-?, CTX attenuated inflammatory responses by preserving epithelial barrier integrity, maintaining ZO-1 expression and reducing ICAM-1 expression and IL-8 secretion. Furthermore, IFN-?-stimulated Caco-2 cultures induced neutrophil and monocyte migration, an effect reduced when CTX was present. The TNBS intrarectal instillation in mice induced acute colitis, which was ameliorated by CTX administration resulting in reduced weight loss, lower clinical scores, smaller necrotic areas, decreased recruitment of neutrophils, monocytes and macrophages into the lamina propria, and a partial reversal of TNBS-induced gut dysbiosis. Notably, the protective effects of CTX were abrogated by Boc 2 , an antagonist of formyl peptide receptor (FPR), indicating the role of these receptors on the effect of CTX. In conclusion, CTX prevents early events of acute colitis by regulating epithelial and immune responses and modulating the gut microbiota through FPR-mediated pathways, highlighting its promise as a novel therapeutic candidate.
Introduction:
The intestinal epithelium is crucial as the first barrier against the entry of pathogens and for the maintenance of local homeostasis. The epithelial cell layer establishes direct contact with the external environment and is continuously exposed to viruses, fungi, parasites, and potentially pathogenic bacteria ( 1 , 2 ) Selective permeability of this epithelium is mediated by two distinct pathways: transcellular and paracellular. The transcellular pathway is responsible for the absorption of sugars, amino acids,…
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