Interleukin-10 receptor signaling through XXXX regulates the apoptosis of @entity2479 cells in response to stress.

@entity2308 @entity2479 @entity19 @entity13358 @entity12001 @entity619 @entity35
PURPOSE: @entity13358 has recently been shown to promote survival of neurons and glia. The purpose of this report is to investigate whether @entity13358 has any role in protecting @entity2479 cells (RGCs) from death under conditions in which growth factors are removed, or in which oxidative stress is present. Signal transduction pathways that activate @entity13358 signaling in RGCs were studied in both stress conditions. METHODS: Effects of various interleukins on the viability of the RGC cell line was determined, and apoptotic cells were quantified. Immunoblot analysis was preformed to identify the @entity13358 receptor (IL-10R) and phosphorylated or nonphosphorylated @entity2308 and @entity12001 proteins in RGC extracts. Immunohistochemistry was performed on the @entity35 retinal sections to identify native IL-10R. RESULTS: Apoptosis of RGCs in the absence of growth factors with or without @entity619 (1 microM) occurred in @entity19 .4% and 53.4% +/- 2.6% of cells, respectively, after 96 hours. Addition of @entity13358 at a concentration of 50 ng/mL significantly reduced the apoptotic population of RGCs to 28.2% +/- 2.3% in the absence of growth factors with @entity619 and to 31% +/- 2.7% in the absence of growth factors alone. RGCs as well as native retina expressed functional IL-10R as determined by immunoblot analysis and by the ability of @entity13358 to phosphorylate @entity12001 . However, @entity13358 failed to phosphorylate @entity2308 in these cells. CONCLUSIONS: @entity13358 caused a 59% and 42% reduction in the apoptotic population of serum-deprived cells with and without @entity619 treatment, respectively. These observations establish that activation of IL-10R promotes survival of RGCs and this survival-promoting activity is due to @entity13358 signaling through the @entity12001 pathway, which inhibits the cell death and not through the @entity2308 cell survival pathway.
