Mechanisms of the pro-inflammatory action of the thyroid stimulating hormone on human abdominal subcutaneous differentiated adipocytes

Abstract

Subclinical hypthyroidism characterized by elevated thyroid stimulating hormone (TSH) levels with normal thyroid hormone levels, is associated with an increased risk for cardiovascular disease. Human adipocytes express the TSH receptor and may be a bystander target of TSH action. Treatment of human differentiated adipocytes with TSH stimulates interleukin (IL)-6 release through activation of the nuclear factor-kappa B (NF-kappaB) pathway. I identified intermediates implicated in TSH-induced activation of NF-kappaB and is upstream regulator, inhibitor of kappa B (IkappaB) kinase (IKK)beta. My results also suggest that TSH-induced NFkappaB activation and IL-6 production are not dependent on protein kinase A (PKA) activity. Studies demonstrate that protein kinase Cdelta and reactive oxygen species are upstream of IKKbeta/NF-kappaB activation. Furthermore, TSH induces monocyte chemoattractant protein-1 production in an IKKbeta- and PKA-dependent manner. Further analysis of the TSH-induced inflammatory response in human adipocytes will broaden our understanding of TSH action in subclinical hypothyroidism.