title: Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects.
abstract: The protein tyrosine phosphatase, SHP-1, is a negative regulator of proinflammatory signaling and autoimmune disease. We have previously reported reduced SHP-1 expression in peripheral blood leukocytes of subjects with multiple sclerosis (MS). Recent evidence indicates that virus-induced DNA methylation of the SHP-1 promoter is responsible for aberrant silencing of SHP-1 expression and function in hematopoietic cells that might relate to inflammatory diseases. In the present study, bisulfite sequencing of the SHP-1 promoter demonstrated that over a third of MS subjects had abnormally high promoter methylation. As SHP-1 is deficient in MS leukocytes and SHP-1-regulated proinflammatory genes are correspondingly upregulated, we propose that increased SHP-1 promoter methylation may relate in part to decreased SHP-1 expression and increased leukocyte-mediated inflammation in MS.
authors.affiliation: Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kumagai
authors.forename: Bernadette
authors.initials: B
authors.lastname: Kalman
authors.forename: Frank A
authors.initials: FA
authors.lastname: Middleton
authors.forename: Tamara
authors.initials: T
authors.lastname: Vyshkina
authors.forename: Paul T
authors.initials: PT
authors.lastname: Massa
mesh_terms: D019175:DNA Methylation / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000502:physiology; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6