Abstract

We are studying the mechanism by which sphingolipids regulate immunity and inflammation. Our focus has been on sphingosine-1-phosphate (S1P), a bioactive lipid enriched in the vascular and lymphatic systems, and the S1P receptors, found on immune cells and the endothelium. Essential roles for S1P and its receptors have been found for immune system development and homeostasis as well as for the regulation of immune responses and inflammation. In collaborative studies, we have found that i) activation of the S1P1 receptor limits expression of pro-inflammatory cytokine in mouse macrophages and ii) endothelial permeability mediated by angiopoietin-1 is regulated by sphingosine kinase 1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK056015-02
Application #
7734232
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2008
Total Cost
$322,101
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Bonder, Claudine S; Sun, Wai Y; Matthews, Tyson et al. (2009) Sphingosine kinase regulates the rate of endothelial progenitor cell differentiation. Blood 113:2108-17
Hughes, Jeniter E; Srinivasan, Suseela; Lynch, Kevin R et al. (2008) Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages. Circ Res 102:950-8
Wu, Yun-Ping; Mizugishi, Kiyomi; Bektas, Meryem et al. (2008) Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease. Hum Mol Genet 17:2257-64
Kono, Mari; Allende, Maria Laura; Proia, Richard L (2008) Sphingosine-1-phosphate regulation of mammalian development. Biochim Biophys Acta 1781:435-41
Li, Xiaochun; Stankovic, Milena; Bonder, Claudine S et al. (2008) Basal and angiopoietin-1-mediated endothelial permeability is regulated by sphingosine kinase-1. Blood 111:3489-97
Allende, Maria L; Zhou, Dapeng; Kalkofen, Danielle N et al. (2008) S1P1 receptor expression regulates emergence of NKT cells in peripheral tissues. FASEB J 22:307-15
Olivera, Ana; Mizugishi, Kiyomi; Tikhonova, Anastassia et al. (2007) The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity 26:287-97
Olivera, Ana; Urtz, Nicole; Mizugishi, Kiyomi et al. (2006) IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and contributes to mast cell responses. J Biol Chem 281:2515-25
Michaud, Jason; Kohno, Masataka; Proia, Richard L et al. (2006) Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice. FEBS Lett 580:4607-12