Acetate protects against intestinal ischemia-reperfusion injury independent of its cognate free fatty acid 2 receptor
| Autor: | Mike C. L. Wu, Trent M. Woodruff, Philip M. Hansbro, Zoe Schofield, Mark E. Cooper |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Neutrophils Ischemia Pharmacology Acetates Biochemistry Receptors G-Protein-Coupled 03 medical and health sciences Mice 0302 clinical medicine medicine.artery Genetics medicine Animals cardiovascular diseases Superior mesenteric artery Receptor Molecular Biology chemistry.chemical_classification Chemistry Intestinal ischemia Fatty acid medicine.disease Ligand (biochemistry) Intestines Mice Inbred C57BL 030104 developmental biology Neutrophil Infiltration Reperfusion Injury Infiltration (medical) Reperfusion injury 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(8) |
| ISSN: | 1530-6860 |
| Popis: | Free fatty acid 2 receptor (FFA2) is highly expressed on neutrophils and, when activated by its cognate ligand acetate, generates potent anti-inflammatory activities. The roles of FFA2 and acetate have not been explored in ischemia-reperfusion injury (IRI). We therefore examined the function of FFA2 and the therapeutic potential of acetate to reduce tissue injury in an acute model of intestinal IRI. The superior mesenteric artery of wild-type (WT) and FFA2-/- mice was briefly occluded then reperfused following treatment with acetate or vehicle. The absence of FFA2 resulted in intestinal injury similar to that observed in WT mice, indicating a minimal causal role for FFA2 in this model. Acetate treatment to WT mice prior to ischemia profoundly protected the intestine from IRI-induced damage. Amelioration of IRI was also observed, although to a lesser extent, when acetate was administered to FFA2-/- mice demonstrating that certain protective effects of acetate were FFA2-independent. Remarkably, despite the lack of tissue damage following IRI, acetate-treated mice had markedly increased neutrophil infiltration to the reperfused intestine which was dependent on FFA2. These studies reveal a minimal causal role for FFA2 in intestinal IRI but highlight the novel therapeutic potential for acetate in the amelioration of ischemia-mediated tissue damage. |
| Databáze: | OpenAIRE |
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