1,25-Dihydroxyvitamin D3 antagonizes interferon-gamma-induced expression of class II major histocompatibility antigens on thyroid follicular and testicular Leydig cells.
Interferon-gamma (IFN gamma) induces production and expression of major histocompatibility complex class II molecules on both marrow-derived and nonbone marrow-derived cell types. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], a seco-steroid derived from vitamin D3, has previously been reported to enhance such expression alone or together with IFN gamma on a number of monocyte/macrophage tumorigenic lines. In contrast, the present studies have found that 1,25-(OH)2D3 inhibited the ability of IFN gamma to induce class II antigen expression on nontransformed rat thyroid follicular epithelial cells (FRTL-5) and mouse testicular Leydig cells (TM3). Although 1,25-(OH)2D3 inhibited the induction of both IA and IE class II locus products, IFN gamma augmentation of class I major histocompatibility complex antigens was not affected. 1,24-(OH)2D3 and 24,25-(OH)2D3 also inhibited class II induction by IFN gamma. Notably, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-(OH)2D3 receptor, indicating that this antagonistic effect probably requires receptor-ligand interaction. Other steroid hormones, such as hydrocortisone or testosterone, had no inhibitory effect on IFN gamma-induced class II expression on Leydig cells. Additionally, the failure of indomethacin to reverse the effect of 1,25-(OH)2D3 and the finding that exogenous prostaglandin E2 did not inhibit class II induction in these cells indicated that prostaglandins are probably not responsible for this anti-IFN gamma activity. In total, these results suggest that an endocrinological mediator is capable of inhibiting class II induction on resident endocrine tissue populations and, therefore, could help to diminish local CD4+ T-cell recognition of these cells.
Tokuda
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N
Department of Microbiology, University of Miami School of Medicine, Florida 33101.
Mano
T
T
Levy
R B
RB
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004848:Epithelium / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007984:Leydig Cell Tumor; D007985:Leydig Cells / Q000276:immunology*; D008297:Male; D051379:Mice; D051381:Rats; D011994:Recombinant Proteins; D013736:Testicular Neoplasms; D013739:Testosterone / Q000494:pharmacology; D013961:Thyroid Gland / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D013739:Testosterone; D015650:24,25-Dihydroxyvitamin D 3; D007371:Interferon-gamma; D002117:Calcitriol; D006854:Hydrocortisone; D007213:Indomethacin