Thyrocytes isolated from autoimmune-diseased thyroids secrete soluble tumor necrosis factor-R1 that is related to their elevated protein kinase C activity.
Soluble tumor necrosis factor (TNF)-alpha receptors have the potential to modulate TNF-alpha activity during autoimmune thyroiditis. In this study we examined cell-surface TNF-alpha receptors and soluble TNF-alpha 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.
LaBue
M
M
J.L. Pettis Memorial Veterans Medical Center, Research Service-151, Loma Linda, California, USA.
Colburn
K K
KK
Green
L M
LM
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis / Q000502:physiology*; D012016:Reference Values; D013961:Thyroid Gland / Q000473:pathology / Q000502:physiology*; D013967:Thyroiditis, Autoimmune / Q000201:enzymology / Q000503:physiopathology*
D047888:Receptors, Tumor Necrosis Factor, Type I; D011493:Protein Kinase C