Overexpression of phosphorylated STAT-1α in the labial salivary glands of patients with Sjögren's syndrome
Article first published online: 30 OCT 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 54, Issue 11, pages 3476–3484, November 2006
How to Cite
Wakamatsu, E., Matsumoto, I., Yasukochi, T., Naito, Y., Goto, D., Mamura, M., Ito, S., Tsutsumi, A. and Sumida, T. (2006), Overexpression of phosphorylated STAT-1α in the labial salivary glands of patients with Sjögren's syndrome. Arthritis & Rheumatism, 54: 3476–3484. doi: 10.1002/art.22176
- Issue published online: 30 OCT 2006
- Article first published online: 30 OCT 2006
- Manuscript Accepted: 24 JUL 2006
- Manuscript Received: 17 JAN 2006
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.
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.
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.
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.