Down-regulation of Fas-ligand mRNA in Sjogren's syndrome patients with enlarged exocrine glands

作者：Tsuzaka Kensei^*; Matsumoto Yukihiro; Sasaki Yasumasa; Abe Tohru; Tsubota Kazuo; Takeuchi Tsutomu

来源：Autoimmunity, 2007, 40(7): 497-502.

DOI：10.1080/08916930701580320

• Sjogren's syndrome
• apoptosis
• autoimmunity
• autoimmune lymphoproliferative syndrome

We have reported that Sjogren's syndrome (SS) patients with enlarged exocrine glands (EEG) formerly referred to as Mikulicz's disease were defective with Fas-ligand (FasL) expression in PBL and lacrimal glands (LGs). To investigate the mechanisms of reduced FasL expression in SS patients with EEG, FasL mRNA expression level was determined using real-time PCR. The FasL gene promoter region (from -1197 to -3) was also amplified using PCR and specific primers. Expression of the FasL mRNA in the LGs and PBLs of three SS patients with EEG was significantly decreased. Direct sequencing revealed a heterozygous point mutation (-259T/C) in the FasL gene promoter region in one SS patient with EEG. A luminescent beta-galactosidase (beta-gal) reporter assay using a p beta gal Enhancer Vector demonstrated that beta-gal activity from the vector including the mutant (-259C) FasL (p beta gal/mFasL) gene promoter region (735 +/- 42) was similar (p = 0.13) to that from a p beta gal Enhancer Vector without the gene promoter region (603 +/- 66). On the other hand, the beta-gal activity was significantly lower (p < 0.0001) than that from a vector including the wild-type (-259T) FasL (p beta gal/wFasL) (3226 +/- 148). In conclusion, the down-regulation of FasL in SS patients with EEG may be due to transcriptional regulation, and the point mutation at -259T/C in the FasL gene promoter region may lead to the down-regulation of FasL mRNA expression and the lymphoproliferative process observed in SS patients with EEG.

• 出版日期2007