Conclusions
Our findings for the first time directly link activities of the TSH and IL-1 pathways. Furthermore, they identify novel molecular interactions that could be targeted as therapy for TAO.
Objective
The objective of the study was to determine whether TSH regulates IL-1RA in fibrocytes and OFs. Design/setting/participants: Fibrocytes and OFs were collected and analyzed from healthy individuals and those with GD in an academic clinical practice. Main outcome measures: Real-time PCR, Western blot analysis, reporter gene assays, and cell transfections were performed.
Results
TSH induces the expression of IL-1RA in fibrocytes and GD-OFs. The patterns of induction diverge quantitatively and qualitatively in the two cell types. This results from relatively small effects on gene transcription-related events but a greater influence on secreted IL-1RA and intracellular IL-1RA mRNA stabilities. These actions of TSH are dependent on the intermediate induction of IL-1α and IL-1β. Conclusions: Our findings for the first time directly link activities of the TSH and IL-1 pathways. Furthermore, they identify novel molecular interactions that could be targeted as therapy for TAO.