PMC:1064873 / 18244-19631
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1064873","sourcedb":"PMC","sourceid":"1064873","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1064873","text":"The interaction of IL-10R with IL-10 induces tyrosine phosphorylation and activation of the latent transcription factors STAT1 and STAT3 [3]. Macrophage-specific STAT3-deficient mice demonstrated that STAT3 plays a dominant role in IL-10-mediated anti-inflammatory responses [5], which has recently been confirmed in human macrophages by studies of dominant-negative STAT3 overexpression [30]. The induction of STAT1 and STAT3 phosphorylation by IL-10 in PB CD4+ T cells from active RA patients and from healthy controls was examined using western blotting. STAT3 phosphorylation was dose-dependently induced after IL-10 activation for 20 min in normal CD4+ T cells (Fig. 4a,4b). In contrast, STAT3 was phosphorylated in freshly isolated PB CD4+ cells from RA patients and this STAT3 phosphorylation was detectable for up to 6 hours. STAT3 phosphorylation was augmented only when activated by as much as 10 ng/ml IL-10. Both sustained STAT3 phosphorylation and defective IL-10-induced STAT3 phosphorylation were found in RA ST CD4+ T cells (Fig. 4c). On the other hand, IL-10-induced STAT1 phosphorylation was not detected in either RA CD4+ T cells or normal CD4+ T cells (Fig. 4a). These results indicate that STAT3 is the major IL-10-activated STAT in CD4+ T cells, and IL-10-induced STAT3 activation may be diminished in active RA, in association with sustained STAT3 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