PI3K/AKT Pathway Mediates Induction of IL-1RA by TSH in Fibrocytes: Modulation by PTEN

摘要

Context:TSH provokes expression of inflammatory genes in CD34~(+) fibrocytes. These cells appear to infiltrate the orbit in Graves' disease (GD), where they putatively become the CD34~(+) orbital fibroblast subset (GD-OF). This may have importance in solving the pathogenesis of thyroid-associated ophthalmopathy. The IL-1 family is targeted by TSH in fibrocytes and OFs by inducing secreted IL-1 receptor antagonist (IL-1RA) and intracellular IL-1RA in a cell-specific pattern. Phosphoinositide 3-kinase (PI3K) mediates several TSH actions in thyroid. This pathway is modulated by phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Vanishingly little is known currently about TSHR signaling to IL-1RA expression in nonthyroidal cells. Furthermore, factors modulating TSH action in these cells are largely unexplored.