Abstract
Soluble tumor necrosis factor (TNF)-α receptors have the potential to modulate TNF-α activity during autoimmune thyroiditis. In this study we examined cell-surface TNF-α receptors and soluble TNF-α receptor production by thyrocytes from normal and MRL-lpr-/- (diseased) mice, which spontaneously develop autoimmune thyroiditis. We found that murine thyrocytes possess the 55-kd receptor(TNF-R1). Examination of soluble TNF-R1 production revealed that diseased thyrocytes produced sevenfold more soluble TNF-R1 than normal thyrocytes. Furthermore, basal protein kinase C (pKC) activity in diseased thyrocytes was 67% higher than that found in normal murine thyrocytes. The elevated basal pKC activity in diseased thyrocytes was related to their enhanced production of soluble TNF-R1 because inhibition of pKC activity with calphostin C caused soluble TNF-R1 production to decrease significantly. Additionally, soluble TNF-R1 production by murine thyrocytes was not a result of cell-surface receptor shedding but through secretion of a truncated version of TNF-R1. This was evident when cell-surface TNF-R1 levels were unchanged after treatment of diseased thyrocytes with calphostin C. Also, the 28-kd form of TNF-R1, which corresponds to the soluble receptor, was present in the intracellular membranes of the diseased thyrocytes.
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