PMC:1064873 / 22079-23420 JSONTXT

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{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/1064873","sourcedb":"PMC","sourceid":"1064873","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1064873","text":"High expression of SOCS1 mRNA in RA CD4+ T cells\nIL-6 induces two potent inhibitors of JAKs (SOCS1 and SOCS3 proteins) that not only act as mediators of negative feedback inhibition, but also play a major role in crosstalk inhibition by opposing other cytokine-signaling pathways [7]. SOCS3 has recently been shown to specifically inhibit STAT3 activation induced by IL-6 but not by IL-10, thereby regulating the divergent action of IL-6 and IL-10 [8,9]. On the contrary, SOCS1 is able to partially inhibit IL-10-mediated STAT3 activation and cellular responses, as well as IFN-γ-mediated STAT1 activation [32]. To determine whether SOCSs were involved in the defective IL-10-induced STAT3 activation of RA CD4+ T cells, the levels of SOCS1 and SOCS3 mRNA expression in PB CD4+ T cells from active RA patients and from healthy controls were compared by semiquantitative real-time PCR. The RA CD4+ T cells contained higher levels of SOCS1 but lower levels of SOCS3 transcripts than did control CD4+ T cells (Fig. 6a). Constitutive expression of SOCS1 mRNA in RA CD4+ T cells was comparable with the expression in normal CD4+ T cells stimulated by 10 ng/ml IL-6 (Fig. 6b), supporting its functional significance. Defective IL-10-induced STAT3 activation therefore appears to be due at least in part to an abundance of SOCS1 in RA CD4+ T 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