Abstract
Pleuritis is a common initial clinical manifestation of tuberculosis. It is associated with an accumulation of a variety of cytokines in the pleura and pleural fluid. We have recently shown that these proinflammatory cytokines induce the pleural mesothelial cell to produce large amounts of nitric oxide, a nitrogen intermediate that has been shown to have a tuberculocidal effect. TGF-β has also been found in situ in tuberculous effusions and pleural tissues and is thought to suppress the immune response and promote tissue repair. This study examined the effects of TGF-β on cytokine-induced NO synthesis by rat pleural mesothelial cells in vitro. Results demonstrated that TGF-β significantly inhibited NO synthesis and that this inhibition was associated with a proportionate decrease in iNOS mRNA and iNOS protein. Suppression of pleural mesothelial cell NO synthesis by TGF-β may be important in the pathogenesis of tuberculous pleuritis.
Similar content being viewed by others
References
Centers for Disease Control. 1986. Tuberculosis provisional data-United States.MMWR 36:254.
Styblo, K. 1989. Overview and epidemiologic assessment of the current global tuberculosis situation with an emphasis on control in developing countries.Rev. Infect. Dis. 11 (Suppl 2):S339.
Light, R. 1994. Pleural Effusion,In Textbook of Respiratory Medicine, Vol. 2, 2nd edition. W. B. Saunders Company, Philadelphia, pp. 2164–2192.
Barnes, P. F., S. D. Mistry, C. L. Cooper, C. Pirmez, T. H. Rea, andR. L. Modlin. 1989. Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritls.J. Immunol. 142:1114–1119.
Antony, V. B., S. W. Godbey, S. L. Kunkel, J. W. Hott, D. L. Hartman, M. D. Burdick, andR. M. Strieter. 1993. Recruitment of inflammatory cells to the pleural space.J. Immunol. 151:7216–7223.
Barnes, P. F., S. Fong, P. J. Brennan, P. E. Twomey, A. Maderzum, andR. L. Modlin. 1990. Local production of tumor necrosis factor and interferon gamma in tuberculosus pleuritis.J. Immunol. 145:149–154.
Shimokata, K., H. Saka, T. Murate, Y. Hasegawa, andT. Hasegawa. 1991. Cytokine content in pleural effusion comparison between tuberculous and carcinomatous pleurisy.Chest 99:1103–1107.
Kindler, V., A. P. Sappino, G. E. Grau, P. F. Pignet, andP. Vassalli. 1989. The inducing role of tumor necrosis factor in the development of bacteriocidal granulomas during BCG infection.Cell 56:731–740.
Willis, R. S., M. Amiy-Tahmasseb, andJ. J. Ellner. 1990. Induction of interleukin-1 and tumor necrosis factor by mycobacterial proteins: the monocyte Western blot.Proc. Natl. Acad. Sci. 87:3348–3352.
Owens, M. W., andM. B. Grisham. 1993. Nitric oxide synthesis by rat pleural mesothelial cells: Induction by cytokines and lipopolysaccharide.Am. J. Physiol. 265 (Lung Cell Mol. Physiol. 9):L110-L116.
Chan, J., Y. Xing, R. S. Maglliozzo, andB. R. Bloom. 1992. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages.J. Exp. Med. 175:1111–1122.
Maeda, J., T. Ueki, N. Ohkawa, T. Iwahashi, T. Nakano, H. Higashino, andK. Higashino. 1993. Local production and localization of transforming growth factor-beta in tuberculous pleurisy.Clin. Exp. Immunol. 92:32–38.
Dunham, D. M., S. Arkins, C. K. Edward, R. Dantzer III, andK. W. Kelly. 1990. Role of interferon-γ in counteracting the suppressive effects of transforming growth factor-β2 and glucocorticoids on the production of tumor necrosis factor-α.J. Leukocyte Biol. 48:474–481.
Ulich, T. R., S. Yin, K. Gou, E. S. Yi, D. Remick, andJ. D. Castillo. 1991. Intratracheal injection of endotoxin and cytokines. II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation.Am. J. Pathol. 138:1097–1101.
Kekow, J., W. Wachsman, J. A. Cronin, D. A. Carson, andM. Lotz. 1990. Transforming growth factorβ and noncytopathic mechanisms of immunodeficiency in human immunodeficiency virus infection.Proc. Natl. Acad. Sci. U.S.A. 87:8321–8325.
Kehrl, J. H., L. M. Waklefield, A. B. Roberts, M. Alvarez-Mon, R. Derynck, M. B. Sporn, andA. S. Fauci. 1986. Production of transforming growth factorβ by human T lymphocytes and its potential role in the regulation of T cell growth.J. Exp. Med. 163:1037–1050.
Chretien, J., J. Bignon, andA. Hirsch. 1985. Pleural response in inflammation: the pleurae in health and disease.In Lung Biology in Health and Disease, Vol. 30. Marcel Dekker Inc, New York. p. 387–488.
Gabrielson, W. W., B. I. Gerwin, C. C. Harris, A. B. Roberts, M. B. Sporn, andJ. F. Lechner. 1988. Stimulation of DNA synthesis in cultured human mesothelial cells by specific growth factors.FASEB J. 2:2717–2721.
Hott, J. W., J. A. Sparks, S. W. Godbey, andV. B. Antony. 1992. Mesothelial cell response to pleural injury: Thrombin-induced proliferation and chemotaxis of rat pleural mesothelial cells.Am. J. Respir. Cell Mol. Biol. 6:421–425.
Vodovotz, Y., C. Bogdan, C. J. Paik, Q. Xie, C. Nathan. 1993. Mechanisms of suppression of macrophage nitric oxide release by transforming growth factorβ. J. Exp. Med. 178:605–613.
Owens, M. W., andS. R. Grimes. 1993. Pleural mesothelial cell response to inflammation: tumor necrosis factor-induced mitogenesis and collagen synthesis.Am. J. Physiol. 265 (Lung Cell Mol Physiol 9):L382-L388.
Ding, A., C. F. Nathan, J. Graycar, R. Derynck, D. J. Stuehr, andS. Srimal. 1990. Macrophage deactivating factor and transforming growth factors-β1, -β2, and -β3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma.J. Immunol. 145:940–944.
Tsunawali, S., M. Sporn, A. Ding, andC. Nathan. 1988. Deactivation of macrophages by transforming growth factor-β.Nature 334:260.
Junquero, D. C., T. Scott-Burden, V. B. Schini, andP. M. Vanhoutte. 1992. Inhibition of cytokine-induced nitric oxide production by transforming growth factor-β1 in human smooth muscle cells.J. Physiol. 454:451–465.
Nelson, B. J., P. Ralph, S. J. Green, andC. A. Nacy. 1991. Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-β1.J. Immunol. 146:1849–1857.
Pfeilschifter, J., andK. Vosbeck. 1991. Transforming growth factorβ 2 inhibits interleukin1β and tumour necrosis factorα-induction of nitric oxide synthase in rat renal mesangial cells.Biochem. Biophys. Res. Commun. 175:372–379.
Schini, V. B., W. Durante, E. Elizondo, T. Scott-Burden, D. C. Junquero, A. I. Schafer, andP. M. Vanhoutte. 1992. The induction of nitric oxide synthase activity is inhibited by TGF-β 1, PDGFAB, and PDGFBB in vascular smooth muscle cells.Eur. J. Pharmacol. 216:379–383.
Goureau, O., M. Lepoivre, F. Bequet, andY. Courtois. 1993. Differential regulation of inducible nitric oxide synthase by fibroblast growth factors and transforming growth factorβ in bovine retinal pigmented epithelial cells: Inverse correlation with cellular proliferation.Proc. Acad. Sci. U.S.A. 90:4276–4280.
Perrella, M. A., M. Yoshizumi, Z. Fen, J. C. Tsai, C. M. Hsieh, S. Kourembanas, andM. E. Lee. 1994. Transforming growth factor-β1, but not dexamethasone, down-regulates nitric-oxide synthase mRNA after its induction by interleukin-1β in rat smooth muscle cells.J. Biol. Chem. 269:14595–14600.
Stuehr, D. J., andC. F. Nathan. 1989. Nitric oxide. A macrophage produce responsible for cytostasis and respiratory in tumor target cells.J. Exp. Med. 169:1543–1555.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Owens, M.W., Milligan, S.A. & Grisham, M.B. Inhibition of rat pleural mesothelial cell nitric oxide synthesis by transforming growth factor-β1. Inflammation 20, 637–646 (1996). https://doi.org/10.1007/BF01488801
Issue Date:
DOI: https://doi.org/10.1007/BF01488801