title: Down-regulation of Fas-ligand mRNA in Sjögren's syndrome patients with enlarged exocrine glands.
abstract: We have reported that Sjögren'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 pbetagal Enhancer Vector demonstrated that beta-gal activity from the vector including the mutant ( - 259C) FasL (pbetagal/mFasL) gene promoter region (735 +/- 42) was similar (p = 0.13) to that from a pbetagal 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 (pbetagal/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.
authors.affiliation: Division of Rheumatology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan. kentsu@saitama-med.ac.jp
authors.forename: Kensei
authors.initials: K
authors.lastname: Tsuzaka
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Abe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D001773:Blood Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D007765:Lacrimal Apparatus / Q000276:immunology / Q000378:metabolism; D008297:Male; D008882:Mikulicz' Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017354:Point Mutation / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics* / Q000276:immunology
chemical_list: D053222:Fas Ligand Protein; D012333:RNA, Messenger