Journal article
Resveratrol attenuates C5a-induced inflammatory responses in vitro and in vivo by inhibiting phospholipase D and sphingosine kinase activities
The FASEB journal, Vol.23(8), pp.2412-2424
08/01/2009
DOI: 10.1096/fj.09-130542
PMID: 19346296
Abstract
The anti-inflammatory activity of the phytoalexin resveratrol (RSV) was evaluated in C5 anaphylatoxin (C5a)-stimulated 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-inflammatory activity of RSV was a function of inhibition of sphingosine kinase (SphK) activity (IC50 similar to 20 mu M) within 5 min of exposure, its membrane localization, and SphK1-mediated Ca2+ release. As an experimental control, the SphK1 pharmacological inhibitor N,N-dimethyl sphingosine (DMS) was used to compare the inhibitory effect of RSV. We also provide evidence that the SphK inhibitory effect of RSV was mediated via 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 in vivo relevance to these data, C5a-induced 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 1 beta, tumor necrosis factor alpha, interleukin 6, and the chemokine MIP-1 alpha. Taken together, these data demonstrate strong anti-inflammatory activity of RSV in vitro and in vivo 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.-Issuree, P. D. A., Pushparaj, P. N., Pervaiz, S., Melendez, A. J. Resveratrol attenuates C5a-induced inflammatory responses in vitro and in vivo by inhibiting phospholipase D and sphingosine kinase activities. FASEB J. 23, 2412-2424 (2009)
Details
- Title: Subtitle
- Resveratrol attenuates C5a-induced inflammatory responses in vitro and in vivo by inhibiting phospholipase D and sphingosine kinase activities
- Creators
- Priya D. A. Issuree - National University of SingaporePeter N. Pushparaj - National University of SingaporeShazib Pervaiz - National University of SingaporeAlirio J. Melendez - National University of Singapore
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.23(8), pp.2412-2424
- Publisher
- Federation Amer Soc Exp Biol
- DOI
- 10.1096/fj.09-130542
- PMID
- 19346296
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 13
- Grant note
- G0700794 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission MRC G0700794 / Medical Research Council-UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) National Medical Research Council and the Biomedical Research Council, Singapore; National Medical Research Council, Singapore National University of Singapore Academic Research Funds; National University of Singapore
- Language
- English
- Date published
- 08/01/2009
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984359796802771
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