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

Chiharu Kumagai, B. Kálmán, Frank A. Middleton, Tamara Vyshkina, Paul T. Massa

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalJournal of Neuroimmunology
Volume246
Issue number1-2
DOIs
Publication statusPublished - May 15 2012

Fingerprint

Regulator Genes
Methylation
Multiple Sclerosis
Leukocytes
Non-Receptor Type 6 Protein Tyrosine Phosphatase
DNA Methylation
Autoimmune Diseases
Viruses
Inflammation
Genes

Keywords

  • Bisulfite sequencing
  • Epigenetics
  • Immune regulation
  • Multiple sclerosis
  • PBMC
  • Protein tyrosine phosphatase

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects. / Kumagai, Chiharu; Kálmán, B.; Middleton, Frank A.; Vyshkina, Tamara; Massa, Paul T.

In: Journal of Neuroimmunology, Vol. 246, No. 1-2, 15.05.2012, p. 51-57.

Research output: Contribution to journalArticle

Kumagai, Chiharu ; Kálmán, B. ; Middleton, Frank A. ; Vyshkina, Tamara ; Massa, Paul T. / Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects. In: Journal of Neuroimmunology. 2012 ; Vol. 246, No. 1-2. pp. 51-57.
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