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.

journal_name

J Neuroimmunol

authors

Kumagai C,Kalman B,Middleton FA,Vyshkina T,Massa PT

doi

10.1016/j.jneuroim.2012.03.003

subject

Has Abstract

pub_date

2012-05-15 00:00:00

pages

51-7

issue

1-2

eissn

0165-5728

issn

1872-8421

pii

S0165-5728(12)00067-7

journal_volume

246

pub_type

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