1. Docosahexaenoic acid (DHA) promotes recovery from postoperative ileus and the repair of the injured intestinal barrier through mast cell-nerve crosstalk.
- Author
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Yi K, An L, Qi Y, Yang T, Duan Y, Zhao X, Zhang P, Huang X, Su X, Tang Z, and Sun D
- Subjects
- Animals, Mice, Humans, Male, Ganglia, Spinal metabolism, Ganglia, Spinal drug effects, Disease Models, Animal, Coculture Techniques, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Mast Cells drug effects, Mast Cells immunology, Docosahexaenoic Acids pharmacology, Docosahexaenoic Acids therapeutic use, Mice, Inbred C57BL, TRPA1 Cation Channel metabolism, Ileus drug therapy, Ileus immunology, Intestinal Mucosa drug effects, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Intestinal Mucosa metabolism, Interleukin-10 metabolism, Postoperative Complications drug therapy, Postoperative Complications immunology
- Abstract
The objective of this study was to investigate the neuroimmune mechanisms implicated in the enhancement of gastrointestinal function through the administration of oral DHA. Mast cell-deficient mice (Kit
W-sh ) and C57BL/6 mice were used to establish postoperative ileus (POI) models. To further validate our findings, we conducted noncontact coculture experiments involving dorsal root ganglion (DRG) cells, bone marrow-derived mast cells (BMMCs) and T84 cells. Furthermore, the results obtained from investigations conducted on animals and cells were subsequently validated through clinical trials. The administration of oral DHA had ameliorative effects on intestinal barrier injury and postoperative ileus. In a mechanistic manner, the anti-inflammatory effect of DHA was achieved through the activation of transient receptor potential ankyrin 1 (TRPA1) on DRG cells, resulting in the stabilization of mast cells and increasing interleukin 10 (IL-10) secretion in mast cells. Furthermore, the activation of the pro-repair WNT1-inducible signaling protein 1 (WISP-1) signaling pathways by mast cell-derived IL-10 resulted in an enhancement of the intestinal barrier integrity. The current study demonstrated that the neuroimmune interaction between mast cells and nerves played a crucial role in the process of oral DHA improving the intestinal barrier integrity of POI, which further triggered the activation of CREB/WISP-1 signaling in intestinal mucosal cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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