The impact of defective gp130/SOCS3 signaling on the astrocyte response to hyper-IL6 (38.17)
| Autor: | Ricardo F Frausto, Gareth Denyer, Jurgen Scheller, Stefan Rose-John, Brendan J Jenkins, Matthias Ernst, Iain L Campbell |
|---|---|
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 182:38.17-38.17 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.supp.38.17 |
| Popis: | Astrocytes derived from Y757F mutant mice defective in gp130-SHP2/SOCS3 signaling were investigated into their ability to respond to IL-6. Compared with WT astrocytes, Y757F astrocytes treated with hyper-IL6, had higher and more sustained activation of STAT3, while the levels of pY-SHP2 and pERK remained unchanged. Gene expression was investigated by Affymetrix gene chip analysis. At 2 hr, 306 genes were upregulated in WT astrocytes and of these, 28 did not increase in Y757F astrocytes. Of 238 genes upregulated in Y757F astrocytes, 9 were not upregulated in WT astrocytes. Some 99 genes were downregulated in WT astrocytes and of those 55 were not decreased in Y757F astrocytes. In WT astrocytes after 12 hrs the level of expression of many genes was reduced back to or near levels seen in the untreated cells, however, in Y757F astrocytes 109 genes either maintained their 2hr upregulated levels or were further increased. A number of candidate genes upregulated by hyper-IL6 in WT and Y757F astrocytes were not upregulated in astrocytes lacking STAT1. In conclusion, hyper-IL6 stimulated gp-130 SHP2/SOCS3 signaling in astrocytes not only moderates the gp-130-STAT pathway but also directly regulates the transcriptional activity of a number of genes many of which are STAT1-dependent. Support: NSW Spinal Cord Injury and Other Neurological Conditions Project Grant. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|