Dataset: The role of SphK1 in hTNFα induced inflammation
The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine...
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 TNFα and have implicated SphK1/S1P in the development and progression of inflammation. Here we further study the relationship of TNFα and SphK1 using an in vivo model. Transgenic hTNFα 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, mTNFα 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 hTNFα induced inflammatory arthritis, potentially through a novel pathway involving IL-6 and SOCS3. Two wild-type replicates; three replicates of human TNFa transgene overexpression and normal sphingosine kinase 1; three replicates of human TNFa transgene overexpression and sphingosine kinase 1 null.
- Species:
- mouse
- Samples:
- 8
- Source:
- E-GEOD-20152
- Updated:
- Dec.12, 2014
- Registered:
- Nov.11, 2014
Sample | SPHINGOSINE KINASE 1 ACTIVITY | TNFA ACTIVITY |
---|---|---|
GSM505624 | over-expression | |
GSM505624 | over-expression | |
GSM505626 | normal | normal |
GSM505624 | over-expression | |
GSM505626 | normal | normal |
GSM505629 | normal | over-expression |
GSM505629 | normal | over-expression |
GSM505629 | normal | over-expression |