Synergistic effects of recombinant tumour necrosis factor and interferon-gamma on rat thyroid cell growth and Ia antigen expression.
In this study, we have investigated the effects of tumour necrosis factor (TNF), interferon-gamma (IFN-gamma) and interleukin-1 (IL-1) on rat thyroid cells, using the continuously growing, differentiated FRTL5 cell line. No effect on cell growth was found with any cytokine alone, but the combination of TNF and IFN-gamma was cytostatic. These cells were not killed in a 18-hr assay for cytotoxicity, but prolonged incubation (4 days) with TNF and IFN-gamma produced cell detachment and death. Normal rat thyroid cells in primary culture were also susceptible to the combination of TNF and IFN-gamma for 4 days, but not 18 hr. In addition, IFN-gamma treatment induced class II (Ia) antigens on thyroid cells, and this was enhanced by TNF. TNF alone did not cause Ia expression on thyroid cells but did increase the constitutive expression of class I antigens. These results suggest that IFN-gamma and TNF, which are likely to be released by the lymphocytes and macrophages infiltrating the gland in thyroid autoimmunity, may synergize to impair cell growth and produce aberrant Ia antigen expression in thyroiditis. This could be an important mechanism for disease perpetuation.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma