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Evaluation of gender differences in methylation‐sensitive immune gene expression in T cells by cDNA microarray
Author(s) -
Hewagama Anura,
Patel Dipak,
Yarlagadda Sushma,
Strickland Faith M.,
Richardson Bruce C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.825.5
Subject(s) - dna methylation , complementary dna , microarray , gene , immune system , microarray analysis techniques , methylation , microbiology and biotechnology , gene expression , immunology , downregulation and upregulation , peripheral blood mononuclear cell , dna microarray , biology , medicine , cancer research , genetics , in vitro
Previous studies in our laboratory have demonstrated that DNA methylation inhibitor 5‐aza‐2′‐deoxycytidine (5‐aza) demethylates DNA. T cell DNA hypomethylation has been implicated in the pathogenesis of idiopathic and drug‐induced human lupus which is 9 time more common in women than men. The genes affected by DNA hypomethylation are largely unknown. We report here a cDNA microarray analysis of T cell gene expression from men and women after treatment with the 5‐aza. PBMC isolated from 3 men and women were stimulated with PHA for 24hrs. T cells were isolated and cultured with or without 5‐aza for 3 days, then restimulated or not for 6 hr with PMA + ionomycin. We identified at least 268 up‐regulated T cell genes in women upon 5‐Aza treatment. 167 of these upregulated genes were uniquely expressed in women compared to men. CTLA4, IL6R and TNFSF14 were among the immune genes uniquely upregulated in women but not in men by 5‐Aza that were chosen for further study. These studies may provide insight into the molecular basis of autoimmune susceptibility in women. Supported by the National Institutes of Health Grant AR 42525 and the US Department of Veterans Affairs.