Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1995 Jan;84(1):8–15.

Expression of TGF-beta in attenuated Salmonella typhimurium: oral administration leads to the reduction of inflammation, IL-2 and IFN-gamma, but enhancement of IL-10, in carrageenin-induced oedema in mice.

A Ianaro 1, D Xu 1, C A O'Donnell 1, M Di Rosa 1, F Y Liew 1
PMCID: PMC1415173  PMID: 7890306

Abstract

Mice injected with carrageenin in the footpad developed local inflammation which peaked at 48 hr. This was significantly reduced in mice inoculated orally with an attenuated Salmonella construct expressing transforming growth factor-beta (TGF-beta). Administration of the Salmonella construct alone had no effect on inflammation. High levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were secreted by draining lymph node cells from mice injected with carrageenin following stimulation in vitro. Prior inoculation with Salmonella enhanced the production of IL-2 and IFN-gamma from the draining lymph node cells. Administration of the Salmonella-TGF-beta construct significantly inhibited the production of these cytokines. In contrast, IL-10 only was secreted from draining lymph node cells of animals inoculated with the Salmonella-TGF-beta construct. Thus, oral administration of TGF-beta can significantly inhibit local inflammation and alter the cytokine secretion pattern of cells from lymph nodes draining the site of inflammation.

Full text

PDF
14

Images in this article

11Figure 1
on p.11

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen J. B., Manthey C. L., Hand A. R., Ohura K., Ellingsworth L., Wahl S. M. Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta. J Exp Med. 1990 Jan 1;171(1):231–247. doi: 10.1084/jem.171.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Assoian R. K., Sporn M. B. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol. 1986 Apr;102(4):1217–1223. doi: 10.1083/jcb.102.4.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barral-Netto M., Barral A., Brownell C. E., Skeiky Y. A., Ellingsworth L. R., Twardzik D. R., Reed S. G. Transforming growth factor-beta in leishmanial infection: a parasite escape mechanism. Science. 1992 Jul 24;257(5069):545–548. doi: 10.1126/science.1636092. [DOI] [PubMed] [Google Scholar]
  5. Barral A., Barral-Netto M., Yong E. C., Brownell C. E., Twardzik D. R., Reed S. G. Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3442–3446. doi: 10.1073/pnas.90.8.3442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brandes M. E., Allen J. B., Ogawa Y., Wahl S. M. Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals. J Clin Invest. 1991 Mar;87(3):1108–1113. doi: 10.1172/JCI115073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carrier M. J., Chatfield S. N., Dougan G., Nowicka U. T., O'Callaghan D., Beesley J. E., Milano S., Cillari E., Liew F. Y. Expression of human IL-1 beta in Salmonella typhimurium. A model system for the delivery of recombinant therapeutic proteins in vivo. J Immunol. 1992 Feb 15;148(4):1176–1181. [PubMed] [Google Scholar]
  8. Charles I., Dougan G. Gene expression and the development of live enteric vaccines. Trends Biotechnol. 1990 May;8(5):117–121. doi: 10.1016/0167-7799(90)90151-m. [DOI] [PubMed] [Google Scholar]
  9. Cheifetz S., Weatherbee J. A., Tsang M. L., Anderson J. K., Mole J. E., Lucas R., Massagué J. The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors. Cell. 1987 Feb 13;48(3):409–415. doi: 10.1016/0092-8674(87)90192-9. [DOI] [PubMed] [Google Scholar]
  10. Cher D. J., Mosmann T. R. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987 Jun 1;138(11):3688–3694. [PubMed] [Google Scholar]
  11. Chomarat P., Rissoan M. C., Banchereau J., Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med. 1993 Feb 1;177(2):523–527. doi: 10.1084/jem.177.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Fava R. A., Olsen N. J., Postlethwaite A. E., Broadley K. N., Davidson J. M., Nanney L. B., Lucas C., Townes A. S. Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia. J Exp Med. 1991 May 1;173(5):1121–1132. doi: 10.1084/jem.173.5.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fernandez-Botran R., Sanders V. M., Mosmann T. R., Vitetta E. S. Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med. 1988 Aug 1;168(2):543–558. doi: 10.1084/jem.168.2.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  18. Fong T. A., Mosmann T. R. The role of IFN-gamma in delayed-type hypersensitivity mediated by Th1 clones. J Immunol. 1989 Nov 1;143(9):2887–2893. [PubMed] [Google Scholar]
  19. 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]
  20. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  21. Ianaro A., O'Donnell C. A., Di Rosa M., Liew F. Y. A nitric oxide synthase inhibitor reduces inflammation, down-regulates inflammatory cytokines and enhances interleukin-10 production in carrageenin-induced oedema in mice. Immunology. 1994 Jul;82(3):370–375. [PMC free article] [PubMed] [Google Scholar]
  22. Kehrl J. H., Roberts A. B., Wakefield L. M., Jakowlew S., Sporn M. B., Fauci A. S. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol. 1986 Dec 15;137(12):3855–3860. [PubMed] [Google Scholar]
  23. 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]
  24. Kuruvilla A. P., Shah R., Hochwald G. M., Liggitt H. D., Palladino M. A., Thorbecke G. J. Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2918–2921. doi: 10.1073/pnas.88.7.2918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lederberg E. M., Cohen S. N. Transformation of Salmonella typhimurium by plasmid deoxyribonucleic acid. J Bacteriol. 1974 Sep;119(3):1072–1074. doi: 10.1128/jb.119.3.1072-1074.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Like B., Massagué J. The antiproliferative effect of type beta transforming growth factor occurs at a level distal from receptors for growth-activating factors. J Biol Chem. 1986 Oct 15;261(29):13426–13429. [PubMed] [Google Scholar]
  27. Meade R., Askenase P. W., Geba G. P., Neddermann K., Jacoby R. O., Pasternak R. D. Transforming growth factor-beta 1 inhibits murine immediate and delayed type hypersensitivity. J Immunol. 1992 Jul 15;149(2):521–528. [PubMed] [Google Scholar]
  28. Miltenburg A. M., van Laar J. M., de Kuiper R., Daha M. R., Breedveld F. C. T cells cloned from human rheumatoid synovial membrane functionally represent the Th1 subset. Scand J Immunol. 1992 May;35(5):603–610. doi: 10.1111/j.1365-3083.1992.tb03260.x. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Nelson B. J., Ralph P., Green S. J., Nacy C. A. Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-beta 1. J Immunol. 1991 Mar 15;146(6):1849–1857. [PubMed] [Google Scholar]
  31. Poirier T. P., Kehoe M. A., Beachey E. H. Protective immunity evoked by oral administration of attenuated aroA Salmonella typhimurium expressing cloned streptococcal M protein. J Exp Med. 1988 Jul 1;168(1):25–32. doi: 10.1084/jem.168.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Racke M. K., Dhib-Jalbut S., Cannella B., Albert P. S., Raine C. S., McFarlin D. E. Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-beta 1. J Immunol. 1991 May 1;146(9):3012–3017. [PubMed] [Google Scholar]
  33. Rook A. H., Kehrl J. H., Wakefield L. M., Roberts A. B., Sporn M. B., Burlington D. B., Lane H. C., Fauci A. S. Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol. 1986 May 15;136(10):3916–3920. [PubMed] [Google Scholar]
  34. Sadoff J. C., Ballou W. R., Baron L. S., Majarian W. R., Brey R. N., Hockmeyer W. T., Young J. F., Cryz S. J., Ou J., Lowell G. H. Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria. Science. 1988 Apr 15;240(4850):336–338. doi: 10.1126/science.3281260. [DOI] [PubMed] [Google Scholar]
  35. Schlaak J., Hermann E., Ringhoffer M., Probst P., Gallati H., Meyer zum Büschenfelde K. H., Fleischer B. Predominance of Th1-type T cells in synovial fluid of patients with Yersinia-induced reactive arthritis. Eur J Immunol. 1992 Nov;22(11):2771–2776. doi: 10.1002/eji.1830221103. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Strugnell R., Dougan G., Chatfield S., Charles I., Fairweather N., Tite J., Li J. L., Beesley J., Roberts M. Characterization of a Salmonella typhimurium aro vaccine strain expressing the P.69 antigen of Bordetella pertussis. Infect Immun. 1992 Oct;60(10):3994–4002. doi: 10.1128/iai.60.10.3994-4002.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Swain S. L., Huston G., Tonkonogy S., Weinberg A. Transforming growth factor-beta and IL-4 cause helper T cell precursors to develop into distinct effector helper cells that differ in lymphokine secretion pattern and cell surface phenotype. J Immunol. 1991 Nov 1;147(9):2991–3000. [PubMed] [Google Scholar]
  39. Thorbecke G. J., Shah R., Leu C. H., Kuruvilla A. P., Hardison A. M., Palladino M. A. Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7375–7379. doi: 10.1073/pnas.89.16.7375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Wahl S. M., Allen J. B., Costa G. L., Wong H. L., Dasch J. R. Reversal of acute and chronic synovial inflammation by anti-transforming growth factor beta. J Exp Med. 1993 Jan 1;177(1):225–230. doi: 10.1084/jem.177.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Wahl S. M., Hunt D. A., Wong H. L., Dougherty S., McCartney-Francis N., Wahl L. M., Ellingsworth L., Schmidt J. A., Hall G., Roberts A. B. Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J Immunol. 1988 May 1;140(9):3026–3032. [PubMed] [Google Scholar]
  44. Wahl S. M. The role of transforming growth factor-beta in inflammatory processes. Immunol Res. 1991;10(3-4):249–254. doi: 10.1007/BF02919701. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Yang D. M., Fairweather N., Button L. L., McMaster W. R., Kahl L. P., Liew F. Y. Oral Salmonella typhimurium (AroA-) vaccine expressing a major leishmanial surface protein (gp63) preferentially induces T helper 1 cells and protective immunity against leishmaniasis. J Immunol. 1990 Oct 1;145(7):2281–2285. [PubMed] [Google Scholar]
  47. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES