Abstract
Rat mesangial cells were shown to be sensitive to recombinant interferon-gamma (IFN-gamma). IFN-gamma reduced thymidine uptake by these cells and inhibited cell proliferation. Incubation of the cells with 1000 U/ml IFN-gamma decreased thymidine uptake by up to 64% and cell numbers were decreased by 17%. The effects of IFN-gamma were dose and time dependent and were partially reversible by the anti-IFN-gamma monoclonal antibody DB-1. This lymphokine did not reduce incorporation of RNA and protein precursors however. Measurements of 3H-uridine and 3H-leucine incorporation indicated significant increases in RNA and protein synthesis (37% and 45%, respectively) on a per cell basis. The mitogenic effects of IL-1 and platelet-derived growth factor (PDGF) were also susceptible to IFN-gamma-mediated inhibition but the mitogenic response to epidermal growth factor (EGF) was much less sensitive. We conclude that while IFN-gamma may act to modulate the mitogenic signals provided by some factors such as IL-1 and PDGF, the response to EGF appears to be unaffected.
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Selected References
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- Carpenter G., Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. doi: 10.1146/annurev.bi.48.070179.001205. [DOI] [PubMed] [Google Scholar]
- Collart M. A., Belin D., Vassalli J. D., de Kossodo S., Vassalli P. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med. 1986 Dec 1;164(6):2113–2118. doi: 10.1084/jem.164.6.2113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doi T., Striker L. J., Elliot S. J., Conti F. G., Striker G. E. Insulinlike growth factor-1 is a progression factor for human mesangial cells. Am J Pathol. 1989 Feb;134(2):395–404. [PMC free article] [PubMed] [Google Scholar]
- Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
- Friesel R., Komoriya A., Maciag T. Inhibition of endothelial cell proliferation by gamma-interferon. J Cell Biol. 1987 Mar;104(3):689–696. doi: 10.1083/jcb.104.3.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gajewski T. F., Fitch F. W. Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4245–4252. [PubMed] [Google Scholar]
- Hancock W. W., Becker G. J., Atkins R. C. A comparison of fixatives and immunohistochemical technics for use with monoclonal antibodies to cell surface antigens. Am J Clin Pathol. 1982 Dec;78(6):825–831. doi: 10.1093/ajcp/78.6.825. [DOI] [PubMed] [Google Scholar]
- Hooke D. H., Gee D. C., Atkins R. C. Leukocyte analysis using monoclonal antibodies in human glomerulonephritis. Kidney Int. 1987 Apr;31(4):964–972. doi: 10.1038/ki.1987.93. [DOI] [PubMed] [Google Scholar]
- Hooke D. H., Hancock W. W., Gee D. C., Kraft N., Atkins R. C. Monoclonal antibody analysis of glomerular hypercellularity in human glomerulonephritis. Clin Nephrol. 1984 Oct;22(4):163–168. [PubMed] [Google Scholar]
- Horii Y., Muraguchi A., Iwano M., Matsuda T., Hirayama T., Yamada H., Fujii Y., Dohi K., Ishikawa H., Ohmoto Y. Involvement of IL-6 in mesangial proliferative glomerulonephritis. J Immunol. 1989 Dec 15;143(12):3949–3955. [PubMed] [Google Scholar]
- Hosang M. Recombinant interferon-gamma inhibits the mitogenic effect of platelet-derived growth factor at a level distal to the growth factor receptor. J Cell Physiol. 1988 Mar;134(3):396–404. doi: 10.1002/jcp.1041340310. [DOI] [PubMed] [Google Scholar]
- Ishimura E., Sterzel R. B., Budde K., Kashgarian M. Formation of extracellular matrix by cultured rat mesangial cells. Am J Pathol. 1989 Apr;134(4):843–855. [PMC free article] [PubMed] [Google Scholar]
- Kimball E. S., Fisher M. C., Persico F. J. Potentiation of Balb/3T3 fibroblast proliferative response by interleukin-1 and epidermal growth factor. Cell Immunol. 1988 May;113(2):341–349. doi: 10.1016/0008-8749(88)90032-9. [DOI] [PubMed] [Google Scholar]
- Krishan A. Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J Cell Biol. 1975 Jul;66(1):188–193. doi: 10.1083/jcb.66.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovett D. H., Larsen A. Cell cycle-dependent interleukin 1 gene expression by cultured glomerular mesangial cells. J Clin Invest. 1988 Jul;82(1):115–122. doi: 10.1172/JCI113558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovett D. H., Ryan J. L., Sterzel R. B. Stimulation of rat mesangial cell proliferation by macrophage interleukin 1. J Immunol. 1983 Dec;131(6):2830–2836. [PubMed] [Google Scholar]
- Lovett D. H., Sterzel R. B., Kashgarian M., Ryan J. L. Neutral proteinase activity produced in vitro by cells of the glomerular mesangium. Kidney Int. 1983 Feb;23(2):342–349. doi: 10.1038/ki.1983.25. [DOI] [PubMed] [Google Scholar]
- Lovett D. H., Szamel M., Ryan J. L., Sterzel R. B., Gemsa D., Resch K. Interleukin 1 and the glomerular mesangium. I. Purification and characterization of a mesangial cell-derived autogrowth factor. J Immunol. 1986 May 15;136(10):3700–3705. [PubMed] [Google Scholar]
- MacDonald H. R., Nabholz M. T-cell activation. Annu Rev Cell Biol. 1986;2:231–253. doi: 10.1146/annurev.cb.02.110186.001311. [DOI] [PubMed] [Google Scholar]
- Martin M., Schwinzer R., Schellekens H., Resch K. Glomerular mesangial cells in local inflammation. Induction of the expression of MHC class II antigens by IFN-gamma. J Immunol. 1989 Mar 15;142(6):1887–1894. [PubMed] [Google Scholar]
- Morganelli P. M., Guyre P. M. IFN-gamma plus glucocorticoids stimulate the expression of a newly identified human mononuclear phagocyte-specific antigen. J Immunol. 1988 Apr 1;140(7):2296–2304. [PubMed] [Google Scholar]
- Nickoloff B. J., Basham T. Y., Merigan T. C., Morhenn V. B. Antiproliferative effects of recombinant alpha- and gamma-interferons on cultured human keratinocytes. Lab Invest. 1984 Dec;51(6):697–701. [PubMed] [Google Scholar]
- Nolasco F. E., Cameron J. S., Hartley B., Coelho A., Hildreth G., Reuben R. Intraglomerular T cells and monocytes in nephritis: study with monoclonal antibodies. Kidney Int. 1987 May;31(5):1160–1166. doi: 10.1038/ki.1987.123. [DOI] [PubMed] [Google Scholar]
- Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
- Schlondorff D. The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J. 1987 Oct;1(4):272–281. doi: 10.1096/fasebj.1.4.3308611. [DOI] [PubMed] [Google Scholar]
- Schmiegel W. H., Caesar J., Kalthoff H., Greten H., Schreiber H. W., Thiele H. G. Antiproliferative effects exerted by recombinant human tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human pancreatic tumor cell lines. Pancreas. 1988;3(2):180–188. doi: 10.1097/00006676-198804000-00012. [DOI] [PubMed] [Google Scholar]
- Shultz P. J., DiCorleto P. E., Silver B. J., Abboud H. E. Mesangial cells express PDGF mRNAs and proliferate in response to PDGF. Am J Physiol. 1988 Oct;255(4 Pt 2):F674–F684. doi: 10.1152/ajprenal.1988.255.4.F674. [DOI] [PubMed] [Google Scholar]
- Sterzel R. B., Pabst R. The temporal relationship between glomerular cell proliferation and monocyte infiltration in experimental glomerulonephritis. Virchows Arch B Cell Pathol Incl Mol Pathol. 1982;38(3):337–350. doi: 10.1007/BF02892829. [DOI] [PubMed] [Google Scholar]
- Striker G. E., Striker L. J. Glomerular cell culture. Lab Invest. 1985 Aug;53(2):122–131. [PubMed] [Google Scholar]
- Taetle R., Honeysett J. M. Gamma-interferon modulates human monocyte/macrophage transferrin receptor expression. Blood. 1988 Jun;71(6):1590–1595. [PubMed] [Google Scholar]
- Warner S. J., Friedman G. B., Libby P. Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells. J Clin Invest. 1989 Apr;83(4):1174–1182. doi: 10.1172/JCI113998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Werber H. I., Emancipator S. N., Tykocinski M. L., Sedor J. R. The interleukin 1 gene is expressed by rat glomerular mesangial cells and is augmented in immune complex glomerulonephritis. J Immunol. 1987 May 15;138(10):3207–3212. [PubMed] [Google Scholar]