PMC:1064873 / 19723-21332 JSONTXT

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Both STAT1 and STAT3 phosphorylation was activated by IL-6 in normal CD4+ T cells (data not shown), in agreement with previous observations [4]. Normal CD4+ T cells were thus incubated for 20 min with culture medium containing 30% serum from active RA patients and neutralizing anti-IL-6 antibody or control antibody, and STAT phosphorylation was examined by western blot analysis. RA serum was able to induce tyrosine phosphorylation of STAT3 but not STAT1, and this STAT3 activation was mostly abolished by neutralization of IL-6 activity (Fig. 5a). These results indicate that IL-6 is the dominant STAT3-activating factor contained in sera of active RA patients. The lack of STAT1 activation by RA serum suggests that much higher concentrations of IL-6 may be required for STAT1 activation as compared with STAT3 activation, or that inhibitors of STAT1 signaling may be present in RA 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