A RNA transcript (Heg) in mononuclear cells is negatively correlated with CD14 mRNA and TSH receptor autoantibodies.
During a study of gene expression of foxp3 in blood mononuclear cells we observed a DNA product of an unknown RNA fragment. The area of this peak correlated with CD14 mRNA in a small group of subjects. The sequence was localized to chromosome 1. We tested the hypothesis that gene expression of the poly A(-) transcript (designated Heg) in mononuclear cells was correlated with CD14 mRNA in normal subjects and with CD14 mRNA and TSH receptor autoantibodies in patients with acute and untreated Graves' disease. mRNA was expressed in amol/microg DNA. The main study groups were: (i) normal subjects; (ii) patients with early and untreated Graves' disease; and (iii) patients with Graves' disease studied after treatment. In 18 normal subjects and in 20 patients with treated Graves' disease CD14 mRNA was negatively correlated with Heg (P < 0.001). In 17 untreated patients with Graves' disease Heg and thyroid receptor autoantibodies were negatively correlated (P < 0.009). Incubation studies with mononuclear cells showed that the addition of a fragment of the central part of Heg (949 bases) to mononuclear cells decreased CD14 mRNA markedly to zero or nearly zero (P < 0.001). This response was not specific in the sense that siRNA and lipopolysaccharide also decreased CD14 mRNA, probably due to activation of the CD14/Toll-like receptor complex. Single-stranded RNA is likely to increase interferon production. Due to the anti-inflammatory effect Heg may also inhibit the early phase of TSH receptor autoantibody production.
Christensen
N J
NJ
Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. nijc@heh.regionh.dk
Habekost
G
G
Bratholm
P
P
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011061:Poly A / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000276:immunology*; D014157:Transcription Factors / Q000097:blood*
D001323:Autoantibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011989:Receptors, Thyrotropin; D014157:Transcription Factors; D011061:Poly A
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