title: Effects of type I-interferons on human thyroid epithelial cells derived from normal and tumour tissue.
abstract: Long term interferon (IFN) therapy is frequently associated with side effects which affect the thyroid gland such as hypothyroidism and thyroiditis. We have therefore tested the ability of type I-IFNs to exert direct effects on primary cultures of human thyroid epithelial cells: (i) Type I-IFNs (IFN-alpha 2b and IFN-omega) inhibit cell proliferation as determined by [3H]thymidine incorporation with a half-maximal effect at approximately 1 ng/ml (50 pM). Inhibition of cell growth is observed in cells derived from normal thyroid as well as neoplastic tissue (autonomous and non-secreting adenoma; follicular, papillary and anaplastic carcinoma). (ii) Over a similar concentration range, type I-IFNs suppressed thyroglobulin release by thyroid cells. (iii) IFN-alpha 2b stimulated surface expression of major histocompatibility class (MHC) I but not MHC II molecules, while IFN-gamma enhanced the expression of both MHC I and MHC II molecules. This effect of IFN-gamma, but not that of IFN-alpha 2b was antagonized by suramin. (iv) Incubation of thyroid cells with IFN-alpha 2b also resulted in increased cell surface levels of the intercellular adhesion molecule 1 (ICAM-1). These findings demonstrate that type I-IFNs directly affect thyroid function and explain related side effects of these cytokines. In addition, our results provide a rational basis for the possible use of type I-IFNs in the treatment of patients with advanced thyroid cancer for whom no therapeutic alternative exists.
authors: Institute of Pharmacology, University of Vienna, Austria.
authors: E
authors: E
authors: Selzer
authors: A
authors: A
authors: Wilfing
authors: V
authors: V
authors: Sexl
authors: M
authors: M
authors: Freissmuth
mesh_terms: D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007370:Interferon Type I / Q000494:pharmacology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013964:Thyroid Neoplasms / Q000628:therapy*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C063743:interferon omega 1; D018799:Intercellular Adhesion Molecule-1; D013954:Thyroglobulin