{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:36:26Z","timestamp":1788561386448,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["2951\/2014"],"award-info":[{"award-number":["2951\/2014"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["2951\/2014"],"award-info":[{"award-number":["2951\/2014"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2019,5,20]]},"abstract":"<jats:p>Cardiotonic steroids, such as ouabain and digoxin, are known to bind to Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase and to promote several biological activities, including anti-inflammatory activity. However, there are still no reports in the literature about inflammation and marinobufagenin, a cardiotonic steroid from the bufadienolide family endogenously found in mammals. Therefore, the aim of this work was to analyze,<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>, the role of marinobufagenin in acute inflammation.<jats:italic>Swiss<\/jats:italic>mice were treated with 0.56 mg\/kg of marinobufagenin intraperitoneally (i.p.) and zymosan (2 mg\/mL, i.p.) was used to induce peritoneal inflammation. Peritoneal fluid was collected and used for counting cells by optical microscopy and proinflammatory cytokine quantification (IL-1<jats:italic>\u03b2<\/jats:italic>, IL-6, and TNF-<jats:italic>\u03b1<\/jats:italic>) by immunoenzymatic assay (ELISA). Zymosan stimulation, as expected, induced increased cell migration and proinflammatory cytokine levels in the peritoneum. Marinobufagenin treatment reduced polymorphonuclear cell migration and IL-1<jats:italic>\u03b2<\/jats:italic>and IL-6 levels in the peritoneal cavity, without interfering in TNF-<jats:italic>\u03b1<\/jats:italic>levels. In addition, the effect of marinobufagenin was evaluated using peritoneal macrophages stimulated by zymosan (0.2 mg\/mL)<jats:italic>in vitro<\/jats:italic>. Marinobufagenin treatment at different concentrations (10, 100, 1000, and 10000 nM) showed no cytotoxic effect on peritoneal macrophages. Interestingly, the lowest concentration, which did not inhibit Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase activity, attenuated proinflammatory cytokines IL-1<jats:italic>\u03b2<\/jats:italic>, IL-6, and TNF-<jats:italic>\u03b1<\/jats:italic>levels. To investigate the putative mechanism of action of marinobufagenin, the expression of surface molecules (TLR2 and CD69) and P-p38 MAPK were also evaluated, but no significant effect was observed. Thus, our results suggest that marinobufagenin has an anti-inflammatory role<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>and reveals a novel possible endogenous function of this steroid in mammals.<\/jats:p>","DOI":"10.1155\/2019\/1094520","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T23:30:29Z","timestamp":1558395029000},"page":"1-11","source":"Crossref","is-referenced-by-count":21,"title":["Marinobufagenin Inhibits Neutrophil Migration and Proinflammatory Cytokines"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6987-262X","authenticated-orcid":true,"given":"Deyse C. 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