Endocrinology, Vol 123, 2849-2857, Copyright © 1988 by Endocrine Society

ARTICLES

Effects of rat gamma- and non-gamma-interferons on the expression of Ia antigen, growth, and differentiated functions of FRTL5 cells

T Misaki, D Tramontano and SH Ingbar
Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts 02215.

We undertook the present studies with several objectives in mind: 1) to determine whether recombinant rat gamma-interferon (r gamma IFN) would induce expression of the class II major histocompatibility antigen (Ia) in rat thyroid follicular cells (FRTL5) in culture as human gamma IFN does in cultured human thyrocytes; 2) to characterize the properties of this response, if it does indeed occur; 3) to ascertain whether r gamma IFN has any effect on the growth or differentiated function of FRTL5 cells; and 4) to determine how, if at all, effects of r gamma IFN on the growth and function of FRTL5 cells might be related to expression of the Ia antigen. At concentrations between 1 and 30 U/ml, r gamma IFN induced expression of Ia antigen in a concentration-dependent manner. With a supramaximal concentration of r gamma IFN, Ia antigen first appeared between 4 and 16 h and reached a maximum concentration at about 36 h. After removal of r gamma IFN, the Ia antigen concentration remained constant for about 24 h and then declined, becoming undetectable by 72 h. Induction could not be detected in FRTL5 cells cultured with human gamma IFN, rat non-gamma IFN, Concanavalin-A, phytohemagglutinin, or bovine TSH (bTSH). Over the same range of concentrations that induced the Ia antigen, r gamma IFN proved to be a potent inhibitor of the growth of FRTL5 cells induced by a variety of agents. It produced a concentration-dependent inhibition of the stimulation of [3H] thymidine incorporation and cell replication in FRTL5 cells induced by bTSH. This effect was unaccompanied by any inhibition of either the binding of bTSH to FRTL5 cells or the bTSH- induced increase in cellular cAMP concentration induced therein. However, r gamma IFN did inhibit the stimulation of [3H] thymidine incorporation into DNA induced by (Bu)2cAMP. r gamma IFN also inhibited the stimulation of DNA synthesis and cell replication induced by insulin-like growth factor I (IGF-I) without affecting the specific binding of IGF-I, and decreased the extent of stimulation of [3H]thymidine incorporation induced by the phorbol ester tetradecanoyl phorbol acetate (TPA). Thus, r gamma IFN inhibited both the cAMP- dependent pathway of growth activated by TSH, doing so at some post- cAMP locus, and the cAMP-independent pathways of growth regulation that are activated by IGF-I and TPA.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				A. P. Saavedra, L. A. Cass, G. V. Prendergast, and J. L. Meinkoth Differential Effects of Acute and Chronic Exposure to Interferon-{gamma} on Cyclic Adenosine 3',5'-Monophosphate Response Element-Regulated Gene Expression Endocrinology, February 1, 2000; 141(2): 606 - 614. [Abstract] [Full Text] [PDF]

				A. Miyazaki, H. Shimura, T. Endo, K. Haraguchi, and T. Onaya Tumor Necrosis Factor-{alpha} and Interferon-{gamma} Suppress Both Gene Expression and Deoxyribonucleic Acid-Binding of TTF-2 in FRTL-5 Cells Endocrinology, September 1, 1999; 140(9): 4214 - 4220. [Abstract] [Full Text]

				P. L. Balducci-Silano, K. Suzuki, M. Ohta, J. Saito, M. Ohmori, V. Montani, G. Napolitano, M. Shong, S.-I. Taniguchi, M. Pietrarelli, et al. Regulation of Major Histocompatibility (MHC) Class II Human Leukocyte Antigen-DR{alpha} Gene Expression in Thyrocytes by Single Strand Binding Protein-1, a Transcription Factor That Also Regulates Thyrotropin Receptor and MHC Class I Gene Expression Endocrinology, May 1, 1998; 139(5): 2300 - 2313. [Abstract] [Full Text] [PDF]

				S.-I. Taniguchi, M. Shong, C. Giuliani, G. Napolitano, M. Saji, V. Montani, K. Suzuki, D. S. Singer, and L. D. Kohn Iodide Suppression of Major Histocompatibility Class I Gene Expression in Thyroid Cells Involves Enhancer A and the Transcription Factor NF-{kappa}B Mol. Endocrinol., January 1, 1998; 12(1): 19 - 33. [Abstract] [Full Text]

				V. Montani, S.-i. Taniguchi, M. Shong, K. Suzuki, M. Ohmori, C. Giuliani, G. Napolitano, M. Saji, B. Fiorentino, A. M. Reimold, et al. Major Histocompatibility Class II HLA-DR{alpha} Gene Expression in Thyrocytes: Counter Regulation by the Class II Transactivator and the Thyroid Y Box Protein Endocrinology, January 1, 1998; 139(1): 280 - 289. [Abstract] [Full Text] [PDF]

				V. Montani, M. Shong, S.-i. Taniguchi, K. Suzuki, C. Giuliani, G. Napolitano, J. Saito, M. Saji, B. Fiorentino, A. M. Reimold, et al. Regulation of Major Histocompatibility Class II Gene Expression in FRTL-5 Thyrocytes: Opposite Effects of Interferon and Methimazole Endocrinology, January 1, 1998; 139(1): 290 - 302. [Abstract] [Full Text] [PDF]