{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:14:42Z","timestamp":1793128482827,"version":"4.5.0"},"reference-count":72,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,4,3]],"date-time":"2009-04-03T00:00:00Z","timestamp":1238716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p>\n                    The anti\u2010inflammatory activity of the phytoalexin resveratrol (RSV) was evaluated in C5 anaphylatoxin (C5a)\u2010stimulated primary neutrophils and in a mouse model of acute peritonitis. Pretreatment of human and mouse neutrophils with RSV significantly blocked oxidative burst, leukocyte migration, degranulation, and inflammatory cytokine production. The anti\u2010inflammatory activity of RSV was a function of inhibition of sphingosine kinase (SphK) activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    ~20\u03bcM) within 5 min of exposure, its membrane localization, and SphKl\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release. As an experimental control, the SphKl pharmacological inhibitor AAtdimethyl sphingosine (DMS) was used to compare the inhibitory effect of RSV. We also provide evidence that the SphK inhibitory effect of RSV was mediated\n                    <jats:italic>via<\/jats:italic>\n                    its ability to block phospholipase D (PLD) activity and membrane recruitment. Furthermore, RSV blocked ERK1\/2 phosphorylation, which functioned independently of SphK1 in this study. To provide\n                    <jats:italic>in vivo<\/jats:italic>\n                    relevance to these data, C5a\u2010induced model of acute peritonitis was established, and the effects of prior injection of RSV were investigated. Indeed, prior injection of RSV virtually completely attenuated the effects of C5a on vascular permeability, neutrophil migration, release of interleukin \u03b2, tumor necrosis factor \u03b1, interleukin 6, and the chemokine MIP\u2010la. Taken together, these data demonstrate strong anti\u2010inflammatory activity of RSV\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    and highlight SphK1 as a potential target of this remarkable phytoalexin. These data could have tremendous implications for the clinical use of RSV in inflammatory pathologies.\u2014 Issuree, P. D. A., Pushparaj, P. N., Pervaiz, S., Melendez, A J. Resveratrol attenuates C5a\u2010induced inflammatory responses\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    by inhibiting phospholipase D and sphingosine kinase activities. FASEBJ. 23, 2412\u20132424 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.09-130542","type":"journal-article","created":{"date-parts":[[2009,4,3]],"date-time":"2009-04-03T21:34:06Z","timestamp":1238794446000},"page":"2412-2424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Resveratrol attenuates C5a\u2010induced inflammatory responses\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    by inhibiting phospholipase D and sphingosine kinase activities"],"prefix":"10.1096","volume":"23","author":[{"given":"Priya D. A.","family":"Issuree","sequence":"first","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter N.","family":"Pushparaj","sequence":"additional","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine Singapore"},{"name":"Medicine\u2010Immunology, Infection, and Inflammation Glasgow Biomedical Research Centre University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazib","family":"Pervaiz","sequence":"additional","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine Singapore"},{"name":"NUS Graduate School for Integrative Sciences and Engineering Singapore"},{"name":"Duke\u2010NUS Graduate Medical School National University of Singapore Singapore"},{"name":"Singapore\u2010Massachusetts Institute of Technology Alliance Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alirio J.","family":"Melendez","sequence":"additional","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine Singapore"},{"name":"NUS Graduate School for Integrative Sciences and Engineering Singapore"},{"name":"Medicine\u2010Immunology, Infection, and Inflammation Glasgow Biomedical Research Centre University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.134.5.3325"},{"key":"e_1_2_6_3_1","first-page":"321","article-title":"The structural basis for anaphylatoxin and chemotactic functions of C3a, C4a, and C5a","volume":"1","author":"Hugli T. 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