{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:06:45Z","timestamp":1788930405343,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Succinate is a metabolite involved in chronic inflammatory diseases, regulating macrophages, dendritic cells, and lymphocytes via its receptor SUCNR1 and through intracellular pathways. Our aim was to analyze whether the succinate\u2013SUCNR1 axis modulates the leukocyte\u2013endothelium interactions (L\/EI) that mediate the formation of inflammatory foci in response to a ubiquitous pro-inflammatory cytokine (TNF\u03b1). L\/EI were analyzed in murine cremasteric venules in vivo and between human umbilical endothelial cells (HUVECs) and peripheral blood mononuclear cells (PBMCs) in vitro. We observed that TNF\u03b1 increased the expression of SUCNR1 and that the L\/EI, the proinflammatory cytokines\u2019 upregulation and the NF-\u03baB activation that induced this cytokine were reduced in Sucnr1\u2212\/\u2212 mice in comparison with WT mice. Intrascrotal injection of exogenous succinate did not induce significant proinflammatory effects per se but, combined with TNF\u03b1, allowed a Sucnr1-independent upregulation of pro-inflammatory cytokines. In vitro, the SUCNR1 antagonist NF-56-EJ40 prevented the interactions of PBMCs with TNF\u03b1-treated HUVECs. HUVECs incubated with exogenous succinate presented higher L\/EI but a limited response to TNF\u03b1. SUCNR1 contributes to TNF\u03b1-induced leukocyte\u2013endothelial interactions. However, exogenous administration of high concentrations of this succinate exerts a complex pattern of effects that may include anti-inflammatory actions.<\/jats:p>","DOI":"10.3390\/ijms27177930","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"7930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sucnr1 Mediates Leukocyte\u2013Endothelial Cell Interactions Induced by Tnf\u03b1"],"prefix":"10.3390","volume":"27","author":[{"given":"Sandra","family":"Coll","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1307-6704","authenticated-orcid":false,"given":"Ana","family":"Jar\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Cristina","family":"Bauset","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1957-5854","authenticated-orcid":false,"given":"Dulce C.","family":"Macias-Ceja","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-9962","authenticated-orcid":false,"given":"Dolores","family":"Ortiz-Masi\u00e1","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"Biomedical Research Center for Liver and Digestive Diseases (CIBEREHD), 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Jes\u00fas","family":"Cos\u00edn-Roger","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"Biomedical Research Center for Liver and Digestive Diseases (CIBEREHD), 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Mar\u00eda D.","family":"Barrachina","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"Biomedical Research Center for Liver and Digestive Diseases (CIBEREHD), 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9675-2423","authenticated-orcid":false,"given":"Sara","family":"Calatayud","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"Biomedical Research Center for Liver and Digestive Diseases (CIBEREHD), 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41392-024-01954-6","article-title":"Metabolic regulation of the immune system in health and diseases: Mechanisms and interventions","volume":"9","author":"Hu","year":"2024","journal-title":"Signal Transduct. 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