|  Help  |  About  |  Contact Us

Publication : Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia.

First Author  Nayak D Year  2010
Journal  Neuroscience Volume  166
Issue  1 Pages  132-44
PubMed ID  20036321 Mgi Jnum  J:159736
Mgi Id  MGI:4452323 Doi  10.1016/j.neuroscience.2009.12.020
Citation  Nayak D, et al. (2010) Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia. Neuroscience 166(1):132-44
abstractText  Microglial activation has been implicated as one of the causative factors for neuroinflammation in various neurodegenerative diseases. The sphingolipid metabolic pathway plays an important role in inflammation, cell proliferation, survival, chemotaxis, and immunity in peripheral macrophages. In this study, we demonstrate that sphingosine kinase1 (SphK1), a key enzyme of the sphingolipid metabolic pathway, and its receptors are expressed in the mouse BV2 microglial cells and SphK1 alters the expression and production of proinflammatory cytokines and nitric oxide in microglia treated with lipopolysaccharide (LPS). LPS treatment increased the SphK1 mRNA and protein expression in microglia as revealed by the RT-PCR, Western blot and immunofluorescence. Suppression of SphK1 by its inhibitor, N, N Dimethylsphingosine (DMS), or siRNA resulted in decreased mRNA expression of TNF-alpha, IL-1beta, and iNOS and release of TNF-alpha and nitric oxide (NO) in LPS-activated microglia. Moreover, addition of sphingosine 1 phosphate (S1P), a breakdown product of sphingolipid metabolism, increased the expression levels of TNF-alpha, IL-1beta and iNOS and production of TNF-alpha and NO in activated microglia. Hence to summarize, suppression of SphK1 in activated microglia inhibits the production of proinflammatory cytokines and NO and the addition of exogenous S1P to activated microglia enhances their inflammatory responses. Since the chronic proinflammatory cytokine production by microglia has been implicated in neuroinflammation, modulation of SphK1 and S1P in microglia could be looked upon as a future potential therapeutic method in the control of neuroinflammation in neurodegenerative diseases.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

1 Bio Entities

Trail: Publication

0 Expression