EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON THE THYROID PEROXIDASE CONTENT, DR ANTIGEN EXPRESSION, AND NUMBER OF MICROVILLI IN CULTURED HUMAN THYROCYTES

We investigated the effects of tumor necrosis factor-alpha (TNF-alpha) on the content of thyroid peroxidase (TPO), the induction of DR antigens, and the morphology of human thyrocytes in monolayer culture. The effects of TNF-alpha were also evaluated in combination with interferon-gamma (IFN-gamma). For the detection of TPO and DR antigens, cultured cells were stained with an immunofluorescent technique and analyzed by fluorescent photometry and FACS. IFN-gamma and TNF-alpha each decreased the content of TPO. When given in combination they had an additive action in decreasing the TPO content. TNF-alpha alone did not induce the expression of HLA-DR antigens, but it enhanced the induction of DR-antigens by IFN-gamma. Scanning electron microscopic examination of cultured cells demonstrated that both IFN-gamma and TNF-alpha decreased the number of microvilli on the thyrocyte surface and inhibited the TSH-induced increase in their number. The combination had an additive effect in the absence and presence of TSH. In conclusion, TNF-alpha decreased the content of TPO and the number of microvilli in cultured thyrocytes, acting additively with IFN-gamma. These findings together with enhancing effect of TNF-alpha on IFN-gamma-induced DR expression suggest that TNF-alpha cooperates with IFN-gamma in both physiological function and pathophysiological autoimmunity of the thyroid gland.