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Abstract

Objective

To clarify the molecular mechanisms of Sjögren's syndrome (SS), we analyzed the functional role of the STAT-1 gene, one of the interferon-γ (IFNγ)–inducible genes, in labial salivary glands (LSGs) from SS patients.

Methods

The expression of STAT-1 messenger RNA (mRNA) was examined by real-time polymerase chain reaction (PCR) analysis, and the phosphorylation of STAT-1 protein (Tyr701 and Ser727 pSTAT-1) was investigated by Western blot and immunohistochemical analyses. The expression of IFNγ-inducible 10-kd protein (IP-10), IFN regulatory factor 1 (IRF-1), and Fas was also examined by real-time PCR and immunohistochemical analyses.

Results

STAT-1α and STAT-1β mRNA were highly expressed in LSGs from SS patients. The level of STAT-1α protein in SS LSGs was higher than that in 3 control LSGs, whereas STAT-1β protein was not clearly detected by Western blot analysis. Moreover, Tyr701 and Ser727 pSTAT-1α proteins were specifically detected in SS LSGs. Immunohistochemical analysis showed localization of Tyr701 pSTAT-1 in infiltrating lymphocytes and the adjacent ductal epithelium from SS patients. Ser727 pSTAT-1 was localized only in the ductal epithelium of SS LSGs. The STAT-1–inducible genes IP-10 and IRF-1 and the Fas genes were highly expressed in SS LSGs and were colocalized with Ser727 pSTAT-1–positive, but not Tyr701 pSTAT-1–positive, cells.

Conclusion

We found evidence of the up-regulation of STAT-1α mRNA and protein in LSGs from SS patients, as well as the presence of pSTAT-1α in ductal epithelium from SS patients. Our findings suggest that STAT-1α, especially Ser727 pSTAT-1, may function as a key molecule in the pathogenesis of SS.