Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects

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• 作者：Chiharu Kumagai^a ; Bernadette Kalman^b ; ^d ; Frank A. Middleton^c ; Tamara Vyshkina^e ; Paul T. Massa^a ; ^b ; ^{massap@upstate.edu}
• 关键词：Bisulfite sequencing ; Epigenetics ; Immune regulation ; Multiple sclerosis ; PBMC ; Protein tyrosine phosphatase
• 刊名：Journal of Neuroimmunology
• 出版年：2012
• 期刊代码：32_01655728
• 类别：neu
• 出版时间：15 May, 2012
• 卷：246
• 期：1-2
• 页码：51-57
• 文件大小：406 K

摘要

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.