Biochemical and Biophysical Research Communications
Down-regulation of Sprouty2 via p38 MAPK plays a key role in the induction of cellular apoptosis by tumor necrosis factor-α
Section snippets
Materials and methods
Materials. Unless otherwise indicated, all reagents were purchased from Sigma–Aldrich (St. Louis, MO). EGF and anti-Spry2 antibody were purchased from Upstate Biotechnology (Lake Placid, NY); TNF-α was obtained from R&D Systems (Minneapolis, Minnesota); SB-431542 was purchased from Tocris Biosciences (Ellisville, MO); PD98059, SP600125, SB203580, and BAY 11-7028 were from Calbiochem (San Diego, CA).
Cell culture. Swiss 3T3 cells were obtained from the American Type Culture Collection (Manassas,
TNF-α down-regulates the protein level of Spry2
To study whether the expression of Spry2 can be regulated by TNF-α, cultured Swiss 3T3 cells were treated with different concentrations of TNF-α for 24 h. Samples were then harvested, and total protein was prepared for immunoblot analysis. As shown in Fig. 1A, Spry2 protein levels declined in a dose-dependent manner in response to treatment with 0.02–10 ng/ml TNF-α. The lower limit for detection of the TNF-α effect was 0.2 ng/ml, and the maximum suppression of Spry2 was attained at a TNF-α
Discussion
TGF-β is the first endogenous cytokine showing capability to down-regulate Spry2 [13], and the functional significance of Spry2 down-regulation has been associated with both cancer formation and enhancement of cellular proliferation. Herein, we further showed that Spry2 down-regulation can be induced by another cytokine, TNF-α and plays a critical role in regulating apoptosis.
Cytokines such as TNF-α are able to regulate gene expression via multiple signal transduction pathways. Therefore, we
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