Systematic name M7683
Brief description Genes down-regulated in ankle joints: SPHK1 [GeneID=8877] versus wildtype over-expressing TNF [GeneID=7124].
Full description or abstract The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine kinase 1 activity. SphK1 is a sphingolipid enzyme that converts sphingosine to bioactive sphingosine-1-phosphate (S1P). Recent data suggest a potential relationship between SphK1 and TNF? and have implicated SphK1/S1P in the development and progression of inflammation. Here we further study the relationship of TNF? and SphK1 using an in vivo model. Transgenic hTNF? mice, which develop a spontaneous arthritis (limited to paws) at 20 weeks, were crossed with SphK1 activity null mice (SphK1-/-) to study the development of inflammatory arthritis in the functional absence of SphK1. Results show that hTNF/SphK1-/- have significantly less severity and progression of arthritis and bone erosions as measured through micro-CT images. Additionally, less COX-2 protein, mTNF? transcript levels and fewer Th 17 cells were detected in the joints of hTNF/SphK1-/- compared to hTNF/SphK1+/+ mice. Microarray analysis of the ankle joint showed that hTNF/SphK1-/- mice have increased transcript levels of IL-6 and SOCS3 compared to hTNF/SphK1+/+ mice. Finally, fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1-/- mice compared to hTNF/SphK1+/+ mice. These data show that SphK1 plays a role in hTNF? induced inflammatory arthritis, potentially through a novel pathway involving IL-6 and SOCS3.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 20644167   Authors: Baker DA,Barth J,Chang R,Obeid LM,Gilkeson GS
Exact source GSE20152_3105_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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