Abstract
To investigate the influence of interleukin-lβ (IL-lβ) on airway epithelial cell growth, we measured [3H]thymidine incorporation and cell numbers of cultured porcine tracheal epithelial cells in the presence or absence of human recombinant IL-1β with or without the following: goat antiporcine polyclonal antibody to platelet-derived growth factor (PDGF); IL-1 receptor antagonist; indomethacin; PD-145065, a combined endothelin-A and -B receptor antagonist; BQ-123, an antagonist selective for endothelin-A receptors; or phosphoramidon, an inhibitor, in part, of endothelin-converting enzymes, including neutral endopeptidase. We found that IL-1β stimulated the proliferation of airway epithelial cells, and this response was inhibited by the IL-1 receptor antagonist and by PD-145065 or BQ-123. However, neither indomethacin nor PDGF antibody was influential. The endothelin receptor antagonists also decreased basal thymidine incorporation by these cells as did phosphormidon, although to a lesser degree. Data from radioimmunoassays indicated that phosphormidon reduced the endogenous production of endothelin-1 from the cells, and IL-lβ clearly increased it over time. We conclude that IL-lβ is a stimulant of airway epithelial cell growth, and its mitogenic effects are mediated, in part, by endogenous endothelin-1 production.
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Bevilacqua MP, Pober JS, Wheller ME, Cotran RS, Gimbrone AJ (1985) Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest 76:2003–2009
Broide DH, Lotz M, Cuomo AJ, Coburn DA, Federman EC, Wasserman SI (1992) Cytokines in symptomatic asthma airways. J Allergy Clin Immunol 89:958–967
Broish L, Mascali JJ, Diskuck J, Bean WR, Martin RJ, Rosenwasser LJ (1992) Detection of alveolar macrophage-derived IL-lβ in asthma. J Immunol 149:3078–3082
Dinarello CA (1989) Interleukin-1 and its biologically related cytokines. Adv Immunol 44; 153
Endo T, Uchida Y, Matsumoto H, Suzuki N, Nomura A, Hirata F, Hasegawa S (1992) Regulation of endothelin-1 synthesis in cultured guinea pig airway epithelial cells by various cytokines. Biochem Biophys Res Commun 186:1594–1599
Granowitz EV, Burton DC, Mancilla J, Dinarello CA (1991) Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. J Biol Chem 266:14147–14150
Kupper TS, Lee F, Birchall N, Clark S, Dower S (1988) Interleukin 1 binds to specific receptors on human keratocytes and induces granulocyte-macrophage colony-stimulating factor mRNA and protein. J Clin Invest 82:1787–1793
Lanfrancone L, Boraschi D, Ghiara P, Falini B, Grignani F, Peri G, Mantovani A, Pelicci GP (1992) Human peritoneal mesothelial cells produce many cytokines (granulocyte colony-stimulating factor (CSF), granulocyte-monocyte CSF, macrophage CSF, interleukin-1 (IL-1), and IL-6) and are activated and stimulated to grow by IL-1. Blood 80:2835–2842
Libby P, Warner SJC, Friedman GB (1988) Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest 81:487–498
Libby P, Warner SJC, Salomon RN, Biringyi LK (1988) Production of platelet-derived growth factorlike mitogen by smooth muscle cells from human atheroma. N Engl J Med 318:1493–1498
MacMahon EG, Palomo MA, Moore WM, McDonald JF, Stern MK (1991) Phosphoramidon blocks the pressor activity of big endothelin[l–39] and lowers blood pressure in spontaneously hypertensive rats. Proc Natl Acad Sci USA 88:703–707
Marini M, Soloperto M, Mezzetti M, Fasoli A, Mattoli S (1991) Interleukin-1 binds to specific receptors on human bronchial epithelial cells and up-regulates granulocyte/macrophage colony-stimulating factor synthesis and release. Am J Respir Cell Mol Biol 4:519–524
Matsumura Y, Ikesawa Y, Tsukahara K, Takgoka M, Morimoto S (1991) Conversion of big endothelin-1 to endothelin-1 by two types of metalloproteinases of cultured porcine vascular smooth muscle cells. Biochem Biophys Res Commun 178:899–905
Mattoli S, Colotta F, Fincato G, Mezzetti M, Mantovani A, Patalano F, Fasoli A (1991) Time course of IL-1 and IL-6 synthesis and release in human bronchial epithelial cell cultures exposed to toluene diisocyanate. J Cell Physiol 149:260–268
Mattoli S, Mattoso VL, Solopertro M, Allegra L, Fasoli A (1991) Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic non-allergic asthma. J Allergy Clin Immunol 87:794–802
Mioki Y, Okada K, Ito H, Matsuyama K, Yano M (1991) Endothelin-converting enzymes of bovine carotid artery smooth muscle. Biochem Biophys Res Commun 174:446–451
Murlas CG, Gulati A, Singh G, Najmabadi F (1995) Endothelin stimulates proliferation of normal airway epithelial cells. Biochem Biophys Res Commun 212:953–959
Ohlsteín EH, Arleth A, Bryan H, Elliott JD, Sung CP (1992) The selective endothelin ETa receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis. Eur J Pharmacol 225:347–350
Opgenorth TJ, Wu-Wong JR, Shioshaki K (1992) Endothelin-converting enzymes. FASEB J 6:2653–2659
Palmer JN, Hartogensis WE, Patten M, Fortuin FD, Long CS (1995) Interleukin-lβ induces cardiac myocyte growth but inhibits cardiac fibroblast proliferation in culture. J Clin Invest 95:2555–2564
Rebello S, Thompson EB, Gulati A (1993) Endothelin mechanisms in altered thyroid states in the rat. Eur J Pharmacol 237:9–16
Singh G, Thompson EB, Gulati A (1994) Altered endothelin-1 concentration in brain and peripheral regions during thyroid dysfunction. Pharmacology 49:184–191
Sironi M, Braviario S, Proserpio P, Biondi A, Vecchi A, Van Damme J, Dejana E, Mantovani A (1989) IL-1 stimulates IL-6 production in endothelial cells. J Immunol 142:549–553
Subramanina S, Bray MA (1987) Interleukin 1 releases histamine from human basophils and mast cells in vitro. J Immunol 138:271–278
Swades De, Zelazny ET, Souhrada JF, Souhrada M (1993) Interleukin-lβ stimulates the proliferation of cultured airway smooth muscle cells via platelet-derived growth factor. Am J Respir Cell Mol Biol 9:645–651
Umekawa T, Matsumura Y, Shimura N, Mu S, Tsukahara Y, Takaoka M, Morimoto S (1993) Plateletinduced stimulation of endothelin-1 production and inhibition by phosphoramidon. J Pharmacol Exp Ther 269:860–869
Vijayaraghaven J, Scicli AG, Carretero OA, Slaugher C, Moomaw C, Hersh LB (1990) The hydrolysis of endothelins by neutral endopeptidase 24.11 (enkephalinase). J Biol Chem 265:14150–14155
Wellings RP, Corder R, Warner TD, Cristol JP, Thiemermann C, Vane JR (1994) Evidence from receptor antagonists of an important role for ET receptor-mediated effects of endothelin-1 in the rat kidney. Br J Pharmacol 111:515–520
Wu S, Boyer CM, Whitaker RS, Berchuck A, Wiener JR, Weinberg JB, Bast RC Jr (1993) Tumor necrosis factor-α as an autocrine and paracrine growth factor for ovarian cancer: monokine induction of tumor cell proliferation and tumor necrosis factor-α expression. Cancer Res 53:1939–1944
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Murlas, C.G., Sharma, A.C., Gulati, A. et al. Interleukin-1β increases airway epithelial cell mitogenesis partly by stimulating endothelin-1 production. Lung 175, 117–126 (1997). https://doi.org/10.1007/PL00007559
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DOI: https://doi.org/10.1007/PL00007559