Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1992 Sep;77(1):7–12.

Transforming growth factor-beta enhances interleukin-6 secretion by intestinal epithelial cells.

D W McGee 1, K W Beagley 1, W K Aicher 1, J R McGhee 1
PMCID: PMC1421595  PMID: 1398766

Abstract

Recent reports have suggested that transforming growth factor-beta (TGF-beta) may have an important role in IgA immune responses, e.g. induction of surface IgM+ B cells to commit to IgA. TGF-beta is also an important regulatory cytokine for the maturation of intestinal epithelial cells. Using the IEC-6 rat intestinal epithelial cell line as a model system, TGF-beta 1 was found to enhance interleukin-6 (IL-6) secretion by the IEC-6 cells. The IL-6 was produced in a dose-dependent manner and secretion could be specifically inhibited by an anti-TGF-beta 1 antibody. IL-6 production by the IEC-6 cells was confirmed by using a rabbit anti-mouse IL-6 antibody which completely neutralized the IL-6 present in the IEC-6 cell supernatant. The enhancement of IL-6 secretion was found to involve a low-level enhancement in the expression of RNA for IL-6. The induction of IL-6 secretion was also reversible when TGF-beta was removed. These results suggest that the action of TGF-beta on intestinal epithelial cells may play an important role in immune responses at the intestinal mucosa.

Full text

PDF
7

Images in this article

9Figure 4
on p.9

Selected References

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

  1. Akira S., Hirano T., Taga T., Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990 Aug;4(11):2860–2867. [PubMed] [Google Scholar]
  2. 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]
  3. Anzano M. A., Rieman D., Prichett W., Bowen-Pope D. F., Greig R. Growth factor production by human colon carcinoma cell lines. Cancer Res. 1989 Jun 1;49(11):2898–2904. [PubMed] [Google Scholar]
  4. 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]
  5. Barclay A. N., Mason D. W. Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli. J Exp Med. 1982 Dec 1;156(6):1665–1676. doi: 10.1084/jem.156.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barnard J. A., Beauchamp R. D., Coffey R. J., Moses H. L. Regulation of intestinal epithelial cell growth by transforming growth factor type beta. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1578–1582. doi: 10.1073/pnas.86.5.1578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beagley K. W., Eldridge J. H., Aicher W. K., Mestecky J., Di Fabio S., Kiyono H., McGhee J. R. Peyer's patch B cells with memory cell characteristics undergo terminal differentiation within 24 hours in response to interleukin-6. Cytokine. 1991 Mar;3(2):107–116. doi: 10.1016/1043-4666(91)90030-h. [DOI] [PubMed] [Google Scholar]
  8. Beagley K. W., Eldridge J. H., Lee F., Kiyono H., Everson M. P., Koopman W. J., Hirano T., Kishimoto T., McGhee J. R. Interleukins and IgA synthesis. Human and murine interleukin 6 induce high rate IgA secretion in IgA-committed B cells. J Exp Med. 1989 Jun 1;169(6):2133–2148. doi: 10.1084/jem.169.6.2133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bland P. W., Warren L. G. Antigen presentation by epithelial cells of the rat small intestine. II. Selective induction of suppressor T cells. Immunology. 1986 May;58(1):9–14. [PMC free article] [PubMed] [Google Scholar]
  10. Brandtzaeg P. Role of J chain and secretory component in receptor-mediated glandular and hepatic transport of immunoglobulins in man. Scand J Immunol. 1985 Aug;22(2):111–146. doi: 10.1111/j.1365-3083.1985.tb01866.x. [DOI] [PubMed] [Google Scholar]
  11. Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
  12. Chiu C. P., Moulds C., Coffman R. L., Rennick D., Lee F. Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7099–7103. doi: 10.1073/pnas.85.19.7099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Coffey R. J., Jr, Goustin A. S., Soderquist A. M., Shipley G. D., Wolfshohl J., Carpenter G., Moses H. L. Transforming growth factor alpha and beta expression in human colon cancer lines: implications for an autocrine model. Cancer Res. 1987 Sep 1;47(17):4590–4594. [PubMed] [Google Scholar]
  14. Coffman R. L., Lebman D. A., Shrader B. Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J Exp Med. 1989 Sep 1;170(3):1039–1044. doi: 10.1084/jem.170.3.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Elias J. A., Lentz V., Cummings P. J. Transforming growth factor-beta regulation of IL-6 production by unstimulated and IL-1-stimulated human fibroblasts. J Immunol. 1991 May 15;146(10):3437–3443. [PubMed] [Google Scholar]
  16. Guerne P. A., Carson D. A., Lotz M. IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J Immunol. 1990 Jan 15;144(2):499–505. [PubMed] [Google Scholar]
  17. Heimark R. L., Twardzik D. R., Schwartz S. M. Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science. 1986 Sep 5;233(4768):1078–1080. doi: 10.1126/science.3461562. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Koyama S. Y., Podolsky D. K. Differential expression of transforming growth factors alpha and beta in rat intestinal epithelial cells. J Clin Invest. 1989 May;83(5):1768–1773. doi: 10.1172/JCI114080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kunimoto D. Y., Nordan R. P., Strober W. IL-6 is a potent cofactor of IL-1 in IgM synthesis and of IL-5 in IgA synthesis. J Immunol. 1989 Oct 1;143(7):2230–2235. [PubMed] [Google Scholar]
  22. Kurokowa M., Lynch K., Podolsky D. K. Effects of growth factors on an intestinal epithelial cell line: transforming growth factor beta inhibits proliferation and stimulates differentiation. Biochem Biophys Res Commun. 1987 Feb 13;142(3):775–782. doi: 10.1016/0006-291x(87)91481-1. [DOI] [PubMed] [Google Scholar]
  23. Kvale D., Løvhaug D., Sollid L. M., Brandtzaeg P. Tumor necrosis factor-alpha up-regulates expression of secretory component, the epithelial receptor for polymeric Ig. J Immunol. 1988 May 1;140(9):3086–3089. [PubMed] [Google Scholar]
  24. Lebman D. A., Lee F. D., Coffman R. L. Mechanism for transforming growth factor beta and IL-2 enhancement of IgA expression in lipopolysaccharide-stimulated B cell cultures. J Immunol. 1990 Feb 1;144(3):952–959. [PubMed] [Google Scholar]
  25. Mayer L., Shlien R. Evidence for function of Ia molecules on gut epithelial cells in man. J Exp Med. 1987 Nov 1;166(5):1471–1483. doi: 10.1084/jem.166.5.1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McGee D. W., Aicher W. K., Eldridge J. H., Peppard J. V., Mestecky J., McGhee J. R. Transforming growth factor-beta enhances secretory component and major histocompatibility complex class I antigen expression on rat IEC-6 intestinal epithelial cells. Cytokine. 1991 Nov;3(6):543–550. doi: 10.1016/1043-4666(91)90480-2. [DOI] [PubMed] [Google Scholar]
  27. Mestecky J., McGhee J. R. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol. 1987;40:153–245. doi: 10.1016/s0065-2776(08)60240-0. [DOI] [PubMed] [Google Scholar]
  28. Murthy U., Anzano M. A., Greig R. G. Expression of TGF-alpha/EGF and TGF-beta receptors in human colon carcinoma cell lines. Int J Cancer. 1989 Jul 15;44(1):110–115. doi: 10.1002/ijc.2910440120. [DOI] [PubMed] [Google Scholar]
  29. Northemann W., Braciak T. A., Hattori M., Lee F., Fey G. H. Structure of the rat interleukin 6 gene and its expression in macrophage-derived cells. J Biol Chem. 1989 Sep 25;264(27):16072–16082. [PubMed] [Google Scholar]
  30. Phillips J. O., Everson M. P., Moldoveanu Z., Lue C., Mestecky J. Synergistic effect of IL-4 and IFN-gamma on the expression of polymeric Ig receptor (secretory component) and IgA binding by human epithelial cells. J Immunol. 1990 Sep 15;145(6):1740–1744. [PubMed] [Google Scholar]
  31. Quaroni A., Wands J., Trelstad R. L., Isselbacher K. J. Epithelioid cell cultures from rat small intestine. Characterization by morphologic and immunologic criteria. J Cell Biol. 1979 Feb;80(2):248–265. doi: 10.1083/jcb.80.2.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shirota K., LeDuy L., Yuan S. Y., Jothy S. Interleukin-6 and its receptor are expressed in human intestinal epithelial cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 1990;58(4):303–308. doi: 10.1007/BF02890085. [DOI] [PubMed] [Google Scholar]
  33. Sonoda E., Matsumoto R., Hitoshi Y., Ishii T., Sugimoto M., Araki S., Tominaga A., Yamaguchi N., Takatsu K. Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production. J Exp Med. 1989 Oct 1;170(4):1415–1420. doi: 10.1084/jem.170.4.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Turner M., Chantry D., Feldmann M. Transforming growth factor beta induces the production of interleukin 6 by human peripheral blood mononuclear cells. Cytokine. 1990 May;2(3):211–216. doi: 10.1016/1043-4666(90)90018-o. [DOI] [PubMed] [Google Scholar]
  35. Van Snick J., Cayphas S., Vink A., Uyttenhove C., Coulie P. G., Rubira M. R., Simpson R. J. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679–9683. doi: 10.1073/pnas.83.24.9679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Wahl S. M., McCartney-Francis N., Mergenhagen S. E. Inflammatory and immunomodulatory roles of TGF-beta. Immunol Today. 1989 Aug;10(8):258–261. doi: 10.1016/0167-5699(89)90136-9. [DOI] [PubMed] [Google Scholar]
  38. White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]

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

RESOURCES