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. 1995 Jan;63(1):224–228. doi: 10.1128/iai.63.1.224-228.1995

Induction of transforming growth factor beta 1 by purified protein derivative of Mycobacterium tuberculosis.

Z Toossi 1, T G Young 1, L E Averill 1, B D Hamilton 1, H Shiratsuchi 1, J J Ellner 1
PMCID: PMC172981  PMID: 7806361

Abstract

We examined the ability of purified protein derivative (PPD) of Mycobacterium tuberculosis to induce transforming growth factor beta 1 (TGF-beta 1), a potent immunosuppressive and macrophage-deactivating molecule, in blood monocytes from healthy individuals. TBF-beta 1 activity in PPD-induced monocyte supernatants was identified by Western immunoblot analysis and was not inhibited by polymyxin B, an inhibitor of bacterial lipopolysaccharide (LPS). Furthermore, PPD at equivalent amounts in weight to LPS was as potent in stimulation of monocyte production of TGF-beta 1 at 24 h of culture, as quantified by enzyme-linked immunosorbent assay. The inducing effect of PPD, in contrast to that of LPS, was sustained at later time points of culture (72 h). PPD enhanced the constitutive expression of TGF-beta 1 steady-state mRNA in monocytes at 24 and 48 h of culture. In contrast, neither mycobacterial heat shock protein (64-kDa protein of M.bovis) nor LPS induced TGF-beta 1 mRNA. Decay studies suggested a transcriptional rather than a posttranscriptional effect of PPD on TGF-beta 1 gene expression.

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Selected References

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  1. Assoian R. K., Fleurdelys B. E., Stevenson H. C., Miller P. J., Madtes D. K., Raines E. W., Ross R., Sporn M. B. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. doi: 10.1073/pnas.84.17.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bermudez L. E. Production of transforming growth factor-beta by Mycobacterium avium-infected human macrophages is associated with unresponsiveness to IFN-gamma. J Immunol. 1993 Mar 1;150(5):1838–1845. [PubMed] [Google Scholar]
  3. Bermudez L. E., Young L. S. Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex. J Immunol. 1988 May 1;140(9):3006–3013. [PubMed] [Google Scholar]
  4. Chantry D., Turner M., Abney E., Feldmann M. Modulation of cytokine production by transforming growth factor-beta. J Immunol. 1989 Jun 15;142(12):4295–4300. [PubMed] [Google Scholar]
  5. Chatterjee D., Roberts A. D., Lowell K., Brennan P. J., Orme I. M. Structural basis of capacity of lipoarabinomannan to induce secretion of tumor necrosis factor. Infect Immun. 1992 Mar;60(3):1249–1253. doi: 10.1128/iai.60.3.1249-1253.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Czarniecki C. W., Chiu H. H., Wong G. H., McCabe S. M., Palladino M. A. Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells. J Immunol. 1988 Jun 15;140(12):4217–4223. [PubMed] [Google Scholar]
  7. Ding A., Nathan C. F., Graycar J., Derynck R., Stuehr D. J., Srimal S. Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma. J Immunol. 1990 Aug 1;145(3):940–944. [PubMed] [Google Scholar]
  8. Espevik T., Figari I. S., Shalaby M. R., Lackides G. A., Lewis G. D., Shepard H. M., Palladino M. A., Jr Inhibition of cytokine production by cyclosporin A and transforming growth factor beta. J Exp Med. 1987 Aug 1;166(2):571–576. doi: 10.1084/jem.166.2.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hirsch C. S., Yoneda T., Averill L., Ellner J. J., Toossi Z. Enhancement of intracellular growth of Mycobacterium tuberculosis in human monocytes by transforming growth factor-beta 1. J Infect Dis. 1994 Nov;170(5):1229–1237. doi: 10.1093/infdis/170.5.1229. [DOI] [PubMed] [Google Scholar]
  10. Holter W., Goldman C. K., Casabo L., Nelson D. L., Greene W. C., Waldmann T. A. Expression of functional IL 2 receptors by lipopolysaccharide and interferon-gamma stimulated human monocytes. J Immunol. 1987 May 1;138(9):2917–2922. [PubMed] [Google Scholar]
  11. KAPLOW L. S. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE. Blood. 1965 Aug;26:215–219. [PubMed] [Google Scholar]
  12. Kehrl J. H., Wakefield L. M., Roberts A. B., Jakowlew S., Alvarez-Mon M., Derynck R., Sporn M. B., Fauci A. S. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. doi: 10.1084/jem.163.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Khalil N., Bereznay O., Sporn M., Greenberg A. H. Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation. J Exp Med. 1989 Sep 1;170(3):727–737. doi: 10.1084/jem.170.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Lucas C., Bald L. N., Fendly B. M., Mora-Worms M., Figari I. S., Patzer E. J., Palladino M. A. The autocrine production of transforming growth factor-beta 1 during lymphocyte activation. A study with a monoclonal antibody-based ELISA. J Immunol. 1990 Sep 1;145(5):1415–1422. [PubMed] [Google Scholar]
  16. Lyons R. M., Gentry L. E., Purchio A. F., Moses H. L. Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin. J Cell Biol. 1990 Apr;110(4):1361–1367. doi: 10.1083/jcb.110.4.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miyazono K., Heldin C. H. Role for carbohydrate structures in TGF-beta 1 latency. Nature. 1989 Mar 9;338(6211):158–160. doi: 10.1038/338158a0. [DOI] [PubMed] [Google Scholar]
  18. Miyazono K., Hellman U., Wernstedt C., Heldin C. H. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem. 1988 May 5;263(13):6407–6415. [PubMed] [Google Scholar]
  19. Mulé J. J., Schwarz S. L., Roberts A. B., Sporn M. B., Rosenberg S. A. Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells. Cancer Immunol Immunother. 1988;26(2):95–100. doi: 10.1007/BF00205600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Musso T., Espinoza-Delgado I., Pulkki K., Gusella G. L., Longo D. L., Varesio L. Transforming growth factor beta downregulates interleukin-1 (IL-1)-induced IL-6 production by human monocytes. Blood. 1990 Dec 15;76(12):2466–2469. [PubMed] [Google Scholar]
  21. Ranges G. E., Figari I. S., Espevik T., Palladino M. A., Jr Inhibition of cytotoxic T cell development by transforming growth factor beta and reversal by recombinant tumor necrosis factor alpha. J Exp Med. 1987 Oct 1;166(4):991–998. doi: 10.1084/jem.166.4.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roberts A. B., Kim S. J., Kondaiah P., Jakowlew S. B., Denhez F., Glick A. B., Geiser A. G., Watanabe S., Noma T., Lechleider R. Transcriptional control of expression of the TGF-betas. Ann N Y Acad Sci. 1990;593:43–50. doi: 10.1111/j.1749-6632.1990.tb16098.x. [DOI] [PubMed] [Google Scholar]
  23. Shalaby M. R., Ammann A. J. Suppression of immune cell function in vitro by recombinant human transforming growth factor-beta. Cell Immunol. 1988 Apr 1;112(2):343–350. doi: 10.1016/0008-8749(88)90303-6. [DOI] [PubMed] [Google Scholar]
  24. Silva J. S., Twardzik D. R., Reed S. G. Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factor beta (TGF-beta). J Exp Med. 1991 Sep 1;174(3):539–545. doi: 10.1084/jem.174.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Su H. C., Leite-Morris K. A., Braun L., Biron C. A. A role for transforming growth factor-beta 1 in regulating natural killer cell and T lymphocyte proliferative responses during acute infection with lymphocytic choriomeningitis virus. J Immunol. 1991 Oct 15;147(8):2717–2727. [PubMed] [Google Scholar]
  26. Toossi Z., Sedor J. R., Lapurga J. P., Ondash R. J., Ellner J. J. Expression of functional interleukin 2 receptors by peripheral blood monocytes from patients with active pulmonary tuberculosis. J Clin Invest. 1990 Jun;85(6):1777–1784. doi: 10.1172/JCI114635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tsunawaki S., Sporn M., Ding A., Nathan C. Deactivation of macrophages by transforming growth factor-beta. Nature. 1988 Jul 21;334(6179):260–262. doi: 10.1038/334260a0. [DOI] [PubMed] [Google Scholar]
  29. Twardzik D. R., Mikovits J. A., Ranchalis J. E., Purchio A. F., Ellingsworth L., Ruscetti F. W. Gamma-interferon-induced activation of latent transforming growth factor-beta by human monocytes. Ann N Y Acad Sci. 1990;593:276–284. doi: 10.1111/j.1749-6632.1990.tb16119.x. [DOI] [PubMed] [Google Scholar]
  30. Valone S. E., Rich E. A., Wallis R. S., Ellner J. J. Expression of tumor necrosis factor in vitro by human mononuclear phagocytes stimulated with whole Mycobacterium bovis BCG and mycobacterial antigens. Infect Immun. 1988 Dec;56(12):3313–3315. doi: 10.1128/iai.56.12.3313-3315.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Van Obberghen-Schilling E., Roche N. S., Flanders K. C., Sporn M. B., Roberts A. B. Transforming growth factor beta 1 positively regulates its own expression in normal and transformed cells. J Biol Chem. 1988 Jun 5;263(16):7741–7746. [PubMed] [Google Scholar]
  32. Wahl S. M., Hunt D. A., Bansal G., McCartney-Francis N., Ellingsworth L., Allen J. B. Bacterial cell wall-induced immunosuppression. Role of transforming growth factor beta. J Exp Med. 1988 Oct 1;168(4):1403–1417. doi: 10.1084/jem.168.4.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wahl S. M., Hunt D. A., Wakefield L. M., McCartney-Francis N., Wahl L. M., Roberts A. B., Sporn M. B. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. doi: 10.1073/pnas.84.16.5788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wahl S. M. Transforming growth factor beta (TGF-beta) in inflammation: a cause and a cure. J Clin Immunol. 1992 Mar;12(2):61–74. doi: 10.1007/BF00918135. [DOI] [PubMed] [Google Scholar]
  35. Wallis R. S., Amir-Tahmasseb M., Ellner J. J. Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte western blot. Proc Natl Acad Sci U S A. 1990 May;87(9):3348–3352. doi: 10.1073/pnas.87.9.3348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wallis R. S., Fujiwara H., Ellner J. J. Direct stimulation of monocyte release of interleukin 1 by mycobacterial protein antigens. J Immunol. 1986 Jan;136(1):193–196. [PubMed] [Google Scholar]
  37. Welch G. R., Wong H. L., Wahl S. M. Selective induction of Fc gamma RIII on human monocytes by transforming growth factor-beta. J Immunol. 1990 May 1;144(9):3444–3448. [PubMed] [Google Scholar]

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