Abstract
Transforming growth factor-beta (TGF-β), a multifunctional polypeptide is produced by a wide variety of cells and regulates a broad array of physiological and pathological functions. TGF-β appears to play a central role in pulmonary fibrosis and may contribute to tumor-associated immunosuppression. Alveolar macrophages are a rich source of TGF-β and are intimately involved in lung inflammation. We therefore chose to study TGF-β regulation in murine alveolar macrophages as well as an immortalized peritoneal macrophage cell line (IC-21). Murine macrophages were incubated with cytokines to evaluate their role in regulating TGF-β mRNA expression. We conclude that IFN-α downregulates TGF-β mRNA expression in murine macrophages.
Similar content being viewed by others
References
Nettesheim, P., P. Ferriola, R. Steigerwalt, A. Robertson, andJ. Rundhaug. 1992. The role of growth factors in the regulation of proliferation of tracheobronchial epithelium.Chest 101:23S-24S.
Assoian, R. K., andM. B. Sporn. 1986. Type beta transforming growth factor in human platelets: Release during platelet degranulation and action on vascular smooth muscle cells.J. Cell Biol. 102:1217–1223.
Kehrl, J. H., L. M. Wakefield, A. B. Roberts, S. Jakowlew, M. Alvarez-Mon, R. Derynck, M. B. Sporn, andA. S. Fauci. 1986. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.J. Exp. Med. 163:1037–1050.
Assoian, R. K., B. E. Fleurdelys, H. C. Stevenson, P. J. Miller, D. K. Madtas, E. W. Raines, R. Ross, andM. B. Sporn. 1987. Expression and secretion of type beta transforming growth factor by activated human macrophages.Proc. Natl. Acad. Sci. U.S.A. 84:6020–6024.
Anzano, M. A., A. B. Roberts, andM. B. Sporn. 1986. Anchorage-independent growth of primary rate embryo cells is induced by platelet-derived growth factor and inhibited by type-beta transforming growth factor.J. Cell. Physiol. 126:312–318.
Massague, J., andB. Like. 1985. Cellular receptors for type beta transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines.J. Biol. Chem. 260:2636–2645.
Wakefield, L. M., D. M. Smith, T. Masui, C. C. Harris, andM. B. Sporn. 1987. Distribution and modulation of the cellular receptor for transforming growth factor-beta.J. Cell. Biol. 105:965–975.
Ignotz, R. A., andJ. Massague. 1986. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.J. Biol. Chem. 261:4337–4345.
Varga, J., J. Rosenbloom, andS. A. Jiminez. 1987. Transforming growth factor beta causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts.Biochem. J. 247:597–604.
Madri, J. A., B. M. Pratt, andA. Tucker. 1988. Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix.J. Cell. Biol. 106:1375–1384.
Roberts, A. B., andM. B. Sporn. 1990. In Peptide Growth Factors and Their Receptors. M. B. Sporn, and A. B. Roberts, editors. Springer-Verlag, New York. 419–472.
Zhou, D., A. Munster, andR. A. Winchurch. 1991. Pathologic concentrations of interleukin 6 inhibit T cell responses via induction of activation of TGF-beta.FASEB J. 5:2582–2585.
Castilla, A., J. Prieto, andN. Fausto. 1991. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alpha therapy.N. Engl. J. Med. 324:933–940.
Martyre, M.-C., H. Magdelenat, andF. Calvo. 1991. Interferon-gamma in vivo reverses the increased platelet levels of platelet-derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia.Br. J. Haematol. 77:431–435.
Khalil, N., andA. H. Greenberg. 1991. The role of TGF-beta in pulmonary fibrosis.Ciba Found. Symp. 157:194–207.
Broekelmann, T. J., A. H. Limper, T. V. Colby, andJ. A. McDonald. 1991. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis.Proc. Natl. Acad. Sci. U.S.A. 88:6642–6646.
Huang, M., S. Dhanani, andS. M. Dubinett. 1993. Down-regulation of Interleukin-2 induced Transforming growth factor-beta by interleukin-7.Am. Rev. Resp. Dis. 147:A757.
Roth, M. D., andS. H. Golub. 1989. Inhibition of lymphokine-activated killer cell function by human alveolar macrophages.Cancer Res. 49:4690–4695.
Senior, R. M., E. J. Campbell, andB. Villiger. 1981. In Methods for Studying Mononuclear Phagocytes. D. O. Adams, P. J. Edelson, and H. Koren, editors. Academic Press, New York. 74–75.
Brooks, B., K. Chapman, J. Lawry, A. Meager, andR. C. Rees. 1990. Suppression of lymphokine-activated killer (LAK) cell induction mediated by interleukin-4 and transforming growth factor-beta 1: Effect of addition of exogenous tumor necrosis factor-alpha and interferongamma, and measurement of their exogenous production.Clin. Exp. Immunol. 82:583–589.
Tada, T., S. Ohzeki, K. Utsumi, H. Takiuchi, M. Muramatsu, X.-F. Li, J. Shimizu, H. Fujiwara, andT. Hamaoka. 1991. Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state.J. Immunol. 146:1077–1082.
McCartney-Francis, N., D. Mizel, L. Wong, L. M. Wahl, andS. M. Wahl. 1988. Transforming growth factor-beta as an immunoregulatory molecule.FASEB J. 2:A875.
Khalil, N., O. Bereznay, M. Sporn, andA. H. Greenberg. 1989. Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.J. Exp. Med. 170:727–737.
Kehrl, J. H., A. B. Roberts, L. M. Wakefield, S. Jakowlew, M. B. Sporn, andA. S. Fauci. 1986. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes.J. Immunol. 137:3855–3860.
Kehrl, J. H., A. S. Taylor, G. A. Delsing, A. B. Roberts, M. B. Sporn, andA. S. Fauci. 1989. Further studies of the role of transforming growth factor-beta in human B cell function.J. Immunol. 143:1868–1874.
Ellingsworth, L. R., D. Nakayama, P. Segarini, J. Dasch, P. Carrillo, andW. Waegell. 1988. Transforming growth factor-betas are equipotent growth inhibitors of interleukin-1-induced thymocyte proliferation.Cell Immunol. 114:41–54.
Kim, K. J., J. Abrams, M. Alphonso, M. Pearce, G. J. Thorbecke, andM. A. Palladino. 1990. Role of endogenously produced interleukin-6 as a second signal in murine thymocyte proliferation induced by multiple cytokines: Regulatory effects of transforming growth factor-beta.Cell Immunol. 131:261–271.
Chantry, D., M. Turner, andM. Feldmann. 1989. Interleukin-(murine pre-B cell growth factor/lymphopoietin 1) stimulates thymocyte growth: Regulation by transforming growth factor beta.Eur. J. Immunol. 19:783–786.
Espevik, T., I. S. Figari, M. R. Shalaby, G. A. Lackides, G. D. Lewis, H. M. Shepard, andM. A. Palladino. 1987. Inhibition of cytokine production by cyclosporin A and transforming growth factor beta.J. Exp. Med. 166:571–576.
Rook, A. H., J. H. Kehrl, L. M. Wakefield, A. B. Roberts, M. B. Sporn, D. B. Burlington, H. C. Lane, andA. S. Fauci. 1986. Effects of transforming growth factor beta on the functions of natural killer cells: Depressed cytolytic activity and blunting of interferon responsiveness.J. Immunol. 136:3916–3920.
Ranges, G. E., I. S. Figari, T. Espevik, andM. A. Palladino. 1987. Inhibition of cytotoxic T cell development by transforming growth factor beta and reversal by recombinant tumor necrosis factor alpha.J. Exp. Med. 166:991–998.
Mule, J. J., S. L. Schwarz, A. B. Roberts, M. B. Sporn, andS. A. Rosenberg. 1988. Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells.Cancer Immunol. Immunother. 26:95–100.
Fontana, A., K. Frei, S. Bodmer, E. Hofer, M. H. Schreier, M. A. Palladino, andR. M. Zinkernagel. 1989. Transforming growth factor-beta inhibits the generation of cytotoxic T cells in virus-infected mice.J. Immunol. 143:3230–3234.
Espevik, T., I. S. Figari, G. E. Ranges, andM. A. Palladino. 1988. Transforming growth factor-beta 1 (TGF-beta 1) and recombinant human tumor necrosis factor-alpha reciprocally regulate the generation of lymphokine-activated killer cell activity. Comparison between natural porcine platelet-derived TGF-beta 1 and TGF-beta 2, and recombinant human TGF-beta 1.J. Immunol. 140:2312–2316.
Constam, D. B., J. Philipp, U. V. Malipiero, P. Dijke, M. Schachner, andA. Fontana. 1992. Differential expression of transforming growth factor-beta 1, -beta 2, and -beta 3 by glioblastoma cells, astrocytes, and microglia.J. Immunol. 148:1404–1410.
Glick, A. B., K. C. Flanders, D. Danielpour, S. H. Yuspa, andM. B. Sporn. 1989. Retinoic acid induces transforming growth factor-beta 2 in cultured keratinocytes and mouse epidermis.Cell Regul. 1:87–97.
Akhurst, R. J., F. Fee, andA. Balmain. 1988. Localized production of TGF-beta mRNA in tumor promoter-stimulated mouse epidermis.Nature 33:363–365.
van Obberghen-Schilling, E., N. S. Roche, K. C. Flanders, M. B. Sporn, andA. B. Roberts. 1988. Transforming growth factor beta 1 positively regulates its own expression in normal and transformed cells.J. Biol. Chem. 263:7741–7746.
Geiser, A. G., S. J. Kim, A. B. Roberts, andM. B. Sporn. 1991. Characterization of the mouse transforming growth factor-beta 1 promoter and activation by the Ha-ras oncogene.Mol. Cell Biol. 11:84–92.
Kim, S. J., H. D. Lee, P. D. Robbins, K. Busam, M. B. Sporn, andA. B. Roberts. 1991. Regulation of transforming growth factor beta 1 gene expression by the product of the retino-blastoma-susceptibility gene.Proc. Natl. Acad. Sci. U.S.A. 88:3052–3056.
Kim, S. J., T. S. Winokur, H. D. Lee, D. Danielpour, K. Y. Kim, A. G. Geiser, L. S. Chen, M. B. Sporn, A. B. Roberts, andG. Jay. 1991. Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene.Mol. Cell Biol. 11:5222–5228.
Madisen, L., N. R. Webb, T. M. Rose, H. Marquardt, T. Ikeda, D. Twardzik, S. Seyedin, andA. F. Purchio. 1988. Transforming growth factor-beta 2: cDNA cloning and sequence analysis.DNA 7:1–8.
Kim, S. J., K. Park, D. Koeller, K. Y. Kim, L. M. Wakefield, M. B. Sporn, andA. B. Roberts. 1992. Post-transcriptional regulation of the human TGF-beta 1 gene.J. Biol. Chem. 267:13702–13707.
Author information
Authors and Affiliations
Additional information
This work was supported by the Tobacco-related Disease Research Program (#1KT110), the University of California Cancer Research Coordinating Committee, the Jonsson Cancer Center Foundation and Veterans Administration Merit Review Research Funds. Min Huang was supported by a Jaye Haddad/Concern Foundation Tumor Immunology fellowship.
Rights and permissions
About this article
Cite this article
Dhanani, S., Huang, M., Wang, J. et al. Interferon-alpha inhibits murine macrophage transforming growth factor-beta mRNA expression. Inflammation 18, 301–309 (1994). https://doi.org/10.1007/BF01534271
Issue Date:
DOI: https://doi.org/10.1007/BF01534271