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.