Skip to main content
SpringerLink
Log in

Cyclosporine A inhibits interleukin-8 production in a human colon epithelial cell line (HT-29)

  • Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Intestinal epithelial cells produce various inflammatory mediators. However, the way in which immunosuppressive agents influence the production of these mediators by intestinal epithelial cells is not understood. The effects of cyclosporine A (CsA), tacrolimus (FK506), and dexamethasone (DEX) on cytokin-induced production of interleukin (IL)-8 in a human colonic cancer cell line (HT-29) were examined. HT-29 cells were stimulated with either IL-1β or tumor necrosis factor α (TNFα) together with CsA, FK506, or DEX. The presence of IL-8 protein was detected by enzyme-linked immunosorbent assay, and the expression of IL-8 messenger RNA (mRNA) by reversetranscription polymerase chain reaction. CsA (1, 5, and 10ng/ml) significantly reduced IL-1β-induced IL-8 production (by 32%, 41%, and 48%, respectively), and reduced TNFα-induced IL-8 production (by 21%, 42%, and 50%, respectively). FK506 or DEX had no effect on IL-1β- or TNFα-induced IL-8 production. The expression of IL-8 mRNA was also inhibited by CsA. These findings suggest that CsA may influence the production of inflammatory mediators in colonic cells in a different manner from FK506 and DEX.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dias VC, Shaffer EA, Wallace JI, et al. Bile salts determine leukotriene B4 synthesis in a human intestinal cell line (Caco-2). Dig Dis Sci 1994;39:802–808.

    Article  PubMed  CAS  Google Scholar 

  2. Ferraris L, Karmeli F, Eliakim R, et al. Intestinal epithelial cells contribute to the advanced generation of platelet activating factor in ulcerative colitis. Gut 1993;34:665–668.

    Article  PubMed  CAS  Google Scholar 

  3. Spriggs DR, Imamura K, Rodriguez C, et al. Tumor necrosis factor expression in human epithelial tumor cell lines. J Clin Invest 1988;81:455–460.

    Article  PubMed  CAS  Google Scholar 

  4. Shirota K, LeDuy L, Yuan SY, et al. Interleukin-6 and its receptor are expressed in human intestinal epithelial cells. Virchows Arch B Cell Pathol 1990;58:303–308.

    CAS  Google Scholar 

  5. Hedges, S, Svensson M, Svanborg C. Interleukin-6 response of epithelial cell lines to bacterial stimulation in vitro. Infect Immun 1992;60:1295–1301.

    PubMed  CAS  Google Scholar 

  6. Thomas DM, Nasim MM, Gullick WJ, et al. Immunoreactivity of transforming growth factor alpha in the normal adult gastrointestinal tract. Gut 1992;33:628–631.

    Article  PubMed  CAS  Google Scholar 

  7. van Damme J. Interleukin-8 and related chemotactic cytokines. In: Thomson AW, editor. The cytokine handbook, 2nd ed. London: Academic, 1994:185–208.

    Google Scholar 

  8. Mahida YR, Ceska M, Effenberger F, et al. Enhanced synthesis of neutrophil-activating peptide-I/interleukin-8 in active ulcerative colitis. Clin Sci 1992;82:273–275.

    PubMed  CAS  Google Scholar 

  9. Izzo RS, Witkon K, Chen AI, et al. Neutrophil-activating peptide (interleukin-8) in colonic mucosa from patients with Crohn’s disease. Scand J Gastroenterol 1993;28:296–300.

    Article  PubMed  CAS  Google Scholar 

  10. Saitoh O, Sugi K, Matsuse R, et al. The forms and the levels of fecal PMN-elastase in patients with colorectal diseases. Am J Gastroenterol 1995;90:388–393.

    PubMed  CAS  Google Scholar 

  11. Eckmann L, Jung HC, Schürer-Maly C, et al. Differential cytokine expression by human intestinal epithelial cell lines: Regulated expression of interleukin 8. Gastroenterology 1993; 105:1689–1697.

    PubMed  CAS  Google Scholar 

  12. Jung HC, Eckmann L, Yang S-K, et al. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 1995;95:55–65.

    Article  PubMed  CAS  Google Scholar 

  13. Gross V, Andus T, Daig R, et al. Regulation of interleukin-8 production in a human colon epithelial cell line (HT-29). Gastroenterology 1995;108:653–661.

    Article  PubMed  CAS  Google Scholar 

  14. Sekido N, Mukaida N, Harada A, et al. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature 1993;365:654–657.

    Article  PubMed  CAS  Google Scholar 

  15. Harada A, Sekido N, Kuno K, et al. Expression of recombinant rabbit IL-8 inEscherichia coli and establishment of the essential involvement of IL-8 in recruiting neutrophils into lipopolysaccharide-induced inflammatory site of rabbit skin. Int Immunol 1993;5:681–690.

    Article  PubMed  CAS  Google Scholar 

  16. Fagiuoli S, van Thiel DH. Immunophilin binding agents. In: Rich RR, editor. Clinical immunology. St Louis: Mosby, 1996:1993–2001.

    Google Scholar 

  17. Cash JM, Hoffman GS. Glucocorticoids. In: Rich RR (ed) Clinical immunology. St Louis: Mosby, 1996;1947–1958.

    Google Scholar 

  18. Bos SE, van der Doelen AA, van Rooy N, et al. 3,3′, 5,5′-Tetramethyl benzidine as an Ames test negative chromogen for horseradish peroxidase in enzyme immunoassay. J Immunoassay 1981;2:187–204.

    Article  PubMed  CAS  Google Scholar 

  19. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.

    Article  PubMed  CAS  Google Scholar 

  20. Saitoh O, Nakagawa K, Asada S, et al. Effect of 16, 16-dimethyl prostaglandin E2 on lysosomal membrane stability in rat stomach. J Gastroenterol 1994;29:703–709.

    Article  PubMed  CAS  Google Scholar 

  21. Mazzucchelli L, Hauser C, Zgraggen K, et al. Expression of interleukin-8 gene in inflammatory bowel diseases is related to the histological grade of active inflammation. Am J Pathol 1994;144:977–1007.

    Google Scholar 

  22. Izzo RS, Hadjiyane C, Mir R, et al. In situ reverse transcription PCR of interleukin-8 mRNA in colonic mucosa from patients with active ulcerative colitis. Gastroenterology 1994;106:A705.

    Google Scholar 

  23. Izutani R, Loh EY, Reinecker H-C, et al. Increased expression of interleukin-8 mRNA in ulcerative colitis and Crohn’s disease mucosa and epithelial cells. Inflamm Bowel Dis 1995;1:37–47.

    Article  Google Scholar 

  24. Sandborn WJ. A critical review of cyclosporine therapy in inflammatory bowel diseases. Inflamm Bowel Dis 1995;1:48–63.

    Article  Google Scholar 

  25. Aiko S, Grisham MB. Effects of cyclosporine or FK506 on the pathophysiology observed in a model of chronic granulomatous colitis in rats. Gastroenterology 1995;108:A768.

    Google Scholar 

  26. Sandborn WJ, Strong RM, Forland SC, et al. The pharmacokinetics and colonic tissue concentrations of cyclosporine after IV, oral, and enema administration. J Clin Pharmacol 1991;31:76–80.

    PubMed  CAS  Google Scholar 

  27. Bäckman L, Nigar M, Levy M, et al. FK506 trough levels in whole blood and plasma in liver transplant recipients. Transplantation 1994;57:519–525.

    Article  PubMed  Google Scholar 

  28. Zipfel PF, Bialonski A, Skerka C. Induction of members of the IL-8/NAP-1 gene family in human T lymphocytes is suppressed by cyclosporin A. Biochem Biophys Res Commun 1991;181:179–183.

    Article  PubMed  CAS  Google Scholar 

  29. Mukaida N, Okamoto S, Ishikawa Y, et al. Molecular mechanism of interleukin-8 gene expression. J Leukoc Biol 1994;56:554–558.

    PubMed  CAS  Google Scholar 

  30. Won Y-H, Sauder DN, McKenzie RC. Cyclosporin A inhibits keratinocyte cytokine gene expression. Br J Dermatol 1994;130:312–319.

    Article  PubMed  CAS  Google Scholar 

  31. Hedges S, Agace W, Svensson M, et al. Cyclosporin A does not inhibit IL-1α-induced epithelial cell IL-6 secretion. Scand J Immunol 1993;581–586.

  32. Mukaida N, Gussella GL, Kasahara T, et al. Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line. Immunology 1992;75:674–679.

    PubMed  CAS  Google Scholar 

  33. Chaudhary LR, Avioli LV. Dexamethasone regulates IL-1β and TNFα-induced interleukin-8 production in human bone marrow stromal and osteoblast-like cells. Calcif Tissue Int 1994;55:16–20.

    Article  PubMed  CAS  Google Scholar 

  34. Sarantos P, Abouhamze A, Chakrabarti R, et al. Glucocorticoids regulate intestinal glutamine synthetase gene expression in endotoxemia. Arch Surg 1994;129:59–65.

    PubMed  CAS  Google Scholar 

  35. Sarantos P, Abouhamze A, Copeleand EM, et al. Glucocorticoids regulate glutaminase gene expression in human intestinal epithelial cells. J Surg Res 1994;57:227–231.

    Article  PubMed  CAS  Google Scholar 

  36. Madsen KL, Yanchar NL, Sigalet DL, et al. FK506 increases permeability in rat intestine by inhibiting mitochondrial function. Gastroenterology 1995;109:107–114.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, 569, Takatsuki, Osaka, Japan

    Osamu Saitoh, Kazunori Sugi, Ken Nakagawa, Kentaro Maemura, Keishi Kojima, Ichiro Hirata & Ken-ichi Katsu

  2. Kyoto Medical Science Laboratory, Kyoto, Japan

    Ryoichi Matsuse & Kazuo Uchida

Authors
  1. Osamu Saitoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryoichi Matsuse
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazunori Sugi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ken Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuo Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kentaro Maemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Keishi Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ichiro Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ken-ichi Katsu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saitoh, O., Matsuse, R., Sugi, K. et al. Cyclosporine A inhibits interleukin-8 production in a human colon epithelial cell line (HT-29). J Gastroenterol 32, 605–610 (1997). https://doi.org/10.1007/BF02934109

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02934109

Key words

Search

Navigation