Journal article
Sphingosine kinase-1 (SphK-1) regulates Mycobacterium smegmatis infection in macrophages
H Prakash, A Lüth, N Grinkina, D Holzer, R Wadgaonkar, AP Gonzalez, E Anes, B Kleuser
Plos One | PUBLIC LIBRARY SCIENCE | Published : 2010
Abstract
Sphingosine kinase-1 is known to mediate Mycobacterium smegmatis induced inflammatory responses in macrophages, but its role in controlling infection has not been reported to date. We aimed to unravel the significance of SphK-1 in controlling M. smegmatis infection in RAW 264.7 macrophages. Our results demonstrated for the first time that selective inhibition of SphK-1 by either D, L threo dihydrosphingosine (DHS; a competitive inhibitor of Sphk-1) or Sphk-1 siRNA rendered RAW macrophages sensitive to M. smegmatis infection. This was due to the reduction in the expression of iNOs, p38, pp-38, late phagosomal marker, LAMP-2 and stabilization of the RelA (pp-65) subunit of NF-κB. This led to a..
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Awarded by Portuguese National Foundation for Science
Awarded by Fundação para a Ciência e a Tecnologia
Funding Acknowledgements
This work was supported by the SFB grant from Deutsche Forschungsgemeinschaft (German Research Foundation) and Portuguese National Foundation for Science (PIC/IC/82859/2007; PTDC/SAU-MII/098024/2008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript