Virchows Archiv B

, Volume 58, Issue 1, pp 303–308 | Cite as

Interleukin-6 and its receptor are expressed in human intestinal epithelial cells

  • Kinji Shirota
  • Lam LeDuy
  • Songyang Yuan
  • Serge Jothy


Recent studies have suggested that intestinal epithelial cells demonstrate some of the functions associated with immune competent cells. Based on these observations, we investigated whether gastrointestinal epithelial cells express Interleukin-6 (IL-6). The presence of this cytokine was tested in 53 normal and pathological tissue specimens of the human gastrointestinal tract using an immunohistochemical technique with anti-IL-6 monoclonal and polyclonal antibodies. Immunostaining shows that IL-6 is expressed in gastric and small intestinal epithelial cells. The tumor cells from a large subset (11 of 15) of colon cancer specimens were strongly immunostained. IL-6 immunostaining was less conspicuous and less frequent in the epithelial cells of normal colonic mucosa. Northern blot experiments indicated that the expression of IL-6 in colonic mucosa correlates quantitatively with the presence of its m-RNA. Furthermore, IL-6 receptor (IL-6R) m-RNA was also detected and was twice as abundant in colonie carcinoma as in normal colon. It is concluded that mucosal epithelial cells of the gastrointestinal system express IL-6 and that in the case of the colon, malignancy is accompanied by a higher expression. In addition, the presence of IL-6R transcript suggests that normal and neoplastic colonie epithelial cells might be autocrinally regulated by IL-6.

Key words

Interleukin-6 Epithelial cells m-RNA Immunohistochemistry Colon cancer 


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  1. Campbell IL, Cutri A, Wilson A, Harrison LC (1989) Evidence for IL-6 production by and effects on the pancreatic beta-cell. J Immunol 143:1188–1191PubMedGoogle Scholar
  2. Chirgwin JM, Przybyla AE, Macdonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonucleases. Biochemistry 18:5294–5299PubMedCrossRefGoogle Scholar
  3. Feinberg AP, Vogelstein B (1983) A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13PubMedCrossRefGoogle Scholar
  4. Gibson PR, Van de Pol E, Maxwell LE, Gabriel A, Dow WF (1989) Isolation of colonic crypts that maintain structural and metabolic viability in vitro. Gastroenterology 96:283–291PubMedGoogle Scholar
  5. Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T (1985) Purification to homogeneity and characterization of human B cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA 82:5490–5494PubMedCrossRefGoogle Scholar
  6. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatu A, Tsunasawa S, Sakiyama F, Matsui H, Takahara Y, Taniguchi T, Kishimoto T (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73–76PubMedCrossRefGoogle Scholar
  7. Hirano T, Matsuda T, Hosoi K, Okano A, Matsui H, Kishimoto T (1988) Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2). Immunol Lett 17:41–45PubMedCrossRefGoogle Scholar
  8. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T (1988) Autocrine generation and requirement of BSF-2/ IL-6 for human multiple myelomas. Nature 332:83–85PubMedCrossRefGoogle Scholar
  9. Kirnbauer R, Koeck A, Schwarz T, Urbanski A, Krutmann J, Broth W, Damm D, Shipley G, Ansel JC, Luger TA (1989) IFN-beta 2, B Cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epiderman cells and epidermoid carcinoma cell lines. J Immunol 142:1922–1928PubMedGoogle Scholar
  10. Matsuda T, Hirano T, Kishimoto T (1988) Establishment of interleukin 6 (IL-6/B). Cell stimulatory factor 2 (BSF-2)-dependent cell line and preparation of anti-IL-6/BSF-2 monoclonal antibodies. Eur J Immunol 18:951–956PubMedCrossRefGoogle Scholar
  11. Mayer L, Shlien R (1987) Evidence for function of Ia molecules on gut epithelial cells in man. J Exp Med 166:1471–1483PubMedCrossRefGoogle Scholar
  12. Miki S, Iwano M, Miki Y, Yamamoto M, Tang B, Yokokawa K, Sonoda T, Hirano T, Kishimoto T (1989) Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett 250:607–610PubMedCrossRefGoogle Scholar
  13. Natali PG, DeMartino C, Quaranta V, Nicotra MR, Frezza F, Pelligrino MA, Ferrone S (1981) Expression of la-like antigens in normal human non-lymphoid tissues. Transplantation (Baltimore) 31:75–78Google Scholar
  14. Sternberger LA, Hardy PH, Cululis JJ, Meyer HG (1970) The unlabelled antibody enzyme method of immunohistochemistry, preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-anti-horseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333PubMedGoogle Scholar
  15. Wong GG, Clark SC (1988) Multiple actions of interleukin-6 within a cytokine network. Immunol Today 9:137–139PubMedCrossRefGoogle Scholar
  16. Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988) Cloning and expression of human interleukin 6 (BSF-2/IFNβ2) receptor. Science 241:825–828PubMedCrossRefGoogle Scholar
  17. Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S, Kishimoto T (1987) Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J 6:2939–2945PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Kinji Shirota
    • 1
  • Lam LeDuy
    • 1
  • Songyang Yuan
    • 1
  • Serge Jothy
    • 1
  1. 1.Department of PathologyMcGill UniversityMontrealCanada

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