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 (Tyr^701^ and Ser^727^ 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, Tyr^701^ and Ser^727^ pSTAT‐1α proteins were specifically detected in SS LSGs. Immunohistochemical analysis showed localization of Tyr^701^ pSTAT‐1 in infiltrating lymphocytes and the adjacent ductal epithelium from SS patients. Ser^727^ 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 Ser^727^ pSTAT‐1–positive, but not Tyr^701^ 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 Ser^727^ pSTAT‐1, may function as a key molecule in the pathogenesis of SS.