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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
IL-17 signaling for mRNA stabilization does not require TNF receptor-associated factor 6
Justin Hartupee1, Caini Liu, Michael Novotny
1Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|January 22, 2009
Summary
Interleukin-17 (IL-17) enhances gene expression by stabilizing mRNA, but this process is independent of TNFR-associated factor 6 (TRAF6) and p38 MAPK signaling pathways.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Signaling
Background:
- Interleukin-17 (IL-17) is a cytokine that weakly induces gene expression alone but cooperates with other cytokines like TNF-alpha for a stronger response.
- This cooperation is partly achieved by prolonging mRNA half-life (t1/2).
- TNFR-associated factor 6 (TRAF6) was previously thought to be essential for IL-17 signaling and mRNA stabilization.
Purpose of the Study:
- To investigate the role of TRAF6 in IL-17-mediated mRNA stabilization.
- To determine if TRAF6 or p38 MAPK pathways are involved in IL-17's effect on mRNA stability.
Main Methods:
- Overexpression and dominant-negative inhibition of TRAF6 in HeLa cells.
- Analysis of IL-17-induced mRNA stabilization in TRAF6-deficient and wild-type mouse embryo fibroblasts.
- Inhibition of p38 MAPK and analysis in mice deficient for MAP kinase-activated protein kinase 2/3.
- Assessment of IL-17's effect on TNF-alpha-stimulated mRNAs in wild-type, TRAF6-deficient, and Act1-deficient cells.
Main Results:
- TRAF6 overexpression or inhibition did not affect IL-17-induced KC mRNA stabilization.
- IL-17 stabilized chemokine mRNAs (KC and MIP-2) in both TRAF6-sufficient and TRAF6-deficient cells.
- Inhibition of p38 MAPK and deficiency in MAP kinase-activated protein kinase 2/3 did not block IL-17-mediated mRNA stabilization.
- IL-17-induced mRNA stabilization was dependent on Act1, not TRAF6 or p38 MAPK.
Conclusions:
- A TRAF6/p38 MAPK-independent pathway mediates IL-17 receptor (IL-17R) signaling for enhanced mRNA stability.
- This pathway likely contributes significantly to the potent gene expression responses observed when IL-17 cooperates with cytokines like TNF-alpha.
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