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. 2002 Oct;11(5):313–319. doi: 10.1080/09629350210000015728

Differential expression and upregulation of interleukin-1alpha, interleukin-1beta and interleukin-6 by freshly isolated human small intestinal epithelial cells.

Laura Madrigal-Estebas 1, Derek G Doherty 1, Diarmuid P O'Donoghue 1, Conleth Feighery 1, Cliona O'Farrelly 1
PMCID: PMC1781673  PMID: 12467524

Abstract

BACKGROUND: Small intestinal epithelial cells (SIEC) may contribute to local immune regulation. AIM: To examine production of interleukin (IL)-1alpha, IL-1beta and IL-6 by freshly isolated human SIEC. METHODS: IL-1alpha and IL-1beta mRNA in epithelial layers (EL) prepared from small intestine and in intestinal epithelial cell (EC) lines were examined by reverse transcription-polymerase chain reaction. IL-1alpha, IL-1beta and IL-6 protein expression by SIEC was examined by flow cytometry before and after activation with lipopolysaccharide and epithelial growth factor. RESULTS: IL-1alpha and IL-1beta mRNA was detected in EL and EC lines. Background expression of IL-1alpha and IL-1beta protein by SIEC was observed, which did not increase even following activation. IL-6 protein was expressed by SIEC, in a proportion that increased in two out of three samples following activation. CONCLUSIONS: IL-6 expression and the presence of IL-1alpha and IL-1beta mRNA suggest a role for SIEC in the regulation of local inflammation.

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Selected References

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  1. Atreya R., Mudter J., Finotto S., Müllberg J., Jostock T., Wirtz S., Schütz M., Bartsch B., Holtmann M., Becker C. Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo. Nat Med. 2000 May;6(5):583–588. doi: 10.1038/75068. [DOI] [PubMed] [Google Scholar]
  2. Autschbach F., Braunstein J., Helmke B., Zuna I., Schürmann G., Niemir Z. I., Wallich R., Otto H. F., Meuer S. C. In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease. Am J Pathol. 1998 Jul;153(1):121–130. doi: 10.1016/S0002-9440(10)65552-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Avery A., Paraskeva C., Hall P., Flanders K. C., Sporn M., Moorghen M. TGF-beta expression in the human colon: differential immunostaining along crypt epithelium. Br J Cancer. 1993 Jul;68(1):137–139. doi: 10.1038/bjc.1993.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beil W. J., Weller P. F., Peppercorn M. A., Galli S. J., Dvorak A. M. Ultrastructural immunogold localization of subcellular sites of TNF-alpha in colonic Crohn's disease. J Leukoc Biol. 1995 Sep;58(3):284–298. doi: 10.1002/jlb.58.3.284. [DOI] [PubMed] [Google Scholar]
  5. Challacombe D. N., Wheeler E. E. Trophic action of epidermal growth factor on human duodenal mucosa cultured in vitro. Gut. 1991 Sep;32(9):991–993. doi: 10.1136/gut.32.9.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Cohen-Kaminsky S., Delattre R. M., Devergne O., Rouet P., Gimond D., Berrih-Aknin S., Galanaud P. Synergistic induction of interleukin-6 production and gene expression in human thymic epithelial cells by LPS and cytokines. Cell Immunol. 1991 Nov;138(1):79–93. doi: 10.1016/0008-8749(91)90134-w. [DOI] [PubMed] [Google Scholar]
  8. Daig R., Rogler G., Aschenbrenner E., Vogl D., Falk W., Gross V., Schölmerich J., Andus T. Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6. Gut. 2000 Mar;46(3):350–358. doi: 10.1136/gut.46.3.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Diehl S., Anguita J., Hoffmeyer A., Zapton T., Ihle J. N., Fikrig E., Rincón M. Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1. Immunity. 2000 Dec;13(6):805–815. doi: 10.1016/s1074-7613(00)00078-9. [DOI] [PubMed] [Google Scholar]
  10. Dinarello C. A. Interleukin-1 and interleukin-1 antagonism. Blood. 1991 Apr 15;77(8):1627–1652. [PubMed] [Google Scholar]
  11. Doherty D. G., Norris S., Madrigal-Estebas L., McEntee G., Traynor O., Hegarty J. E., O'Farrelly C. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol. 1999 Aug 15;163(4):2314–2321. [PubMed] [Google Scholar]
  12. Gibson P., Rosella O. Interleukin 8 secretion by colonic crypt cells in vitro: response to injury suppressed by butyrate and enhanced in inflammatory bowel disease. Gut. 1995 Oct;37(4):536–543. doi: 10.1136/gut.37.4.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grottrup-Wolfers E., Moeller J., Karbach U., Muller-Lissner S., Endres S. Elevated cell-associated levels of interleukin 1beta and interleukin 6 in inflamed mucosa of inflammatory bowel disease. Eur J Clin Invest. 1996 Feb;26(2):115–122. doi: 10.1046/j.1365-2362.1996.123262.x. [DOI] [PubMed] [Google Scholar]
  14. Hirano T., Akira S., Taga T., Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today. 1990 Dec;11(12):443–449. doi: 10.1016/0167-5699(90)90173-7. [DOI] [PubMed] [Google Scholar]
  15. Hosokawa T., Kusugami K., Ina K., Ando T., Shinoda M., Imada A., Ohsuga M., Sakai T., Matsuura T., Ito K. Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease. J Gastroenterol Hepatol. 1999 Oct;14(10):987–996. doi: 10.1046/j.1440-1746.1999.01989.x. [DOI] [PubMed] [Google Scholar]
  16. Jarry A., Vallette G., Cassagnau E., Moreau A., Bou-Hanna C., Lemarre P., Letessier E., Le Neel J. C., Galmiche J. P., Laboisse C. L. Interleukin 1 and interleukin 1beta converting enzyme (caspase 1) expression in the human colonic epithelial barrier. Caspase 1 downregulation in colon cancer. Gut. 1999 Aug;45(2):246–251. doi: 10.1136/gut.45.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jones S. C., Trejdosiewicz L. K., Banks R. E., Howdle P. D., Axon A. T., Dixon M. F., Whicher J. T. Expression of interleukin-6 by intestinal enterocytes. J Clin Pathol. 1993 Dec;46(12):1097–1100. doi: 10.1136/jcp.46.12.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jung H. C., Eckmann L., Yang S. K., Panja A., Fierer J., Morzycka-Wroblewska E., Kagnoff M. F. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest. 1995 Jan;95(1):55–65. doi: 10.1172/JCI117676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kunkel E. J., Campbell J. J., Haraldsen G., Pan J., Boisvert J., Roberts A. I., Ebert E. C., Vierra M. A., Goodman S. B., Genovese M. C. Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J Exp Med. 2000 Sep 4;192(5):761–768. doi: 10.1084/jem.192.5.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lionetti P., Pazzaglia A., Moriondo M., Azzari C., Resti M., Amorosi A., Vierucci A. Differing patterns of transforming growth factor-beta expression in normal intestinal mucosa and in active celiac disease. J Pediatr Gastroenterol Nutr. 1999 Sep;29(3):308–313. doi: 10.1097/00005176-199909000-00013. [DOI] [PubMed] [Google Scholar]
  21. Madrigal-Estebas L., McManus R., Byrne B., Lynch S., Doherty D. G., Kelleher D., O'Donoghue D. P., Feighery C., O'Farrelly C. Human small intestinal epithelial cells secrete interleukin-7 and differentially express two different interleukin-7 mRNA Transcripts: implications for extrathymic T-cell differentiation. Hum Immunol. 1997 Dec;58(2):83–90. doi: 10.1016/s0198-8859(97)00230-9. [DOI] [PubMed] [Google Scholar]
  22. Madrigal L., Lynch S., Feighery C., Weir D., Kelleher D., O'Farrelly C. Flow cytometric analysis of surface major histocompatibility complex class II expression on human epithelial cells prepared from small intestinal biopsies. J Immunol Methods. 1993 Feb 3;158(2):207–214. doi: 10.1016/0022-1759(93)90216-t. [DOI] [PubMed] [Google Scholar]
  23. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  24. Opal S. M., DePalo V. A. Anti-inflammatory cytokines. Chest. 2000 Apr;117(4):1162–1172. doi: 10.1378/chest.117.4.1162. [DOI] [PubMed] [Google Scholar]
  25. Panja A., Siden E., Mayer L. Synthesis and regulation of accessory/proinflammatory cytokines by intestinal epithelial cells. Clin Exp Immunol. 1995 May;100(2):298–305. doi: 10.1111/j.1365-2249.1995.tb03668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Papanicolaou D. A., Wilder R. L., Manolagas S. C., Chrousos G. P. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998 Jan 15;128(2):127–137. doi: 10.7326/0003-4819-128-2-199801150-00009. [DOI] [PubMed] [Google Scholar]
  27. Pizarro T. T., Michie M. H., Bentz M., Woraratanadharm J., Smith M. F., Jr, Foley E., Moskaluk C. A., Bickston S. J., Cominelli F. IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells. J Immunol. 1999 Jun 1;162(11):6829–6835. [PubMed] [Google Scholar]
  28. Ramsay A. J., Husband A. J., Ramshaw I. A., Bao S., Matthaei K. I., Koehler G., Kopf M. The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science. 1994 Apr 22;264(5158):561–563. doi: 10.1126/science.8160012. [DOI] [PubMed] [Google Scholar]
  29. Reinecker H. C., Loh E. Y., Ringler D. J., Mehta A., Rombeau J. L., MacDermott R. P. Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology. 1995 Jan;108(1):40–50. doi: 10.1016/0016-5085(95)90006-3. [DOI] [PubMed] [Google Scholar]
  30. Reinecker H. C., MacDermott R. P., Mirau S., Dignass A., Podolsky D. K. Intestinal epithelial cells both express and respond to interleukin 15. Gastroenterology. 1996 Dec;111(6):1706–1713. doi: 10.1016/s0016-5085(96)70036-7. [DOI] [PubMed] [Google Scholar]
  31. Rincón M., Anguita J., Nakamura T., Fikrig E., Flavell R. A. Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells. J Exp Med. 1997 Feb 3;185(3):461–469. doi: 10.1084/jem.185.3.461. [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. Watanabe M., Ueno Y., Yajima T., Iwao Y., Tsuchiya M., Ishikawa H., Aiso S., Hibi T., Ishii H. Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest. 1995 Jun;95(6):2945–2953. doi: 10.1172/JCI118002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Waterhouse C. C., Stadnyk A. W. Rapid expression of IL-1beta by intestinal epithelial cells in vitro. Cell Immunol. 1999 Apr 10;193(1):1–8. doi: 10.1006/cimm.1999.1468. [DOI] [PubMed] [Google Scholar]
  35. Weaver C. T., Unanue E. R. The costimulatory function of antigen-presenting cells. Immunol Today. 1990 Feb;11(2):49–55. doi: 10.1016/0167-5699(90)90018-5. [DOI] [PubMed] [Google Scholar]
  36. Woywodt A., Neustock P., Kruse A., Schwarting K., Ludwig D., Stange E. F., Kirchner H. Cytokine expression in intestinal mucosal biopsies. In situ hybridisation of the mRNA for interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha in inflammatory bowel disease. Eur Cytokine Netw. 1994 Jul-Aug;5(4):387–395. [PubMed] [Google Scholar]
  37. Yamamoto M., Yoshizaki K., Kishimoto T., Ito H. IL-6 is required for the development of Th1 cell-mediated murine colitis. J Immunol. 2000 May 1;164(9):4878–4882. doi: 10.4049/jimmunol.164.9.4878. [DOI] [PubMed] [Google Scholar]
  38. Yang S. K., Eckmann L., Panja A., Kagnoff M. F. Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells. Gastroenterology. 1997 Oct;113(4):1214–1223. doi: 10.1053/gast.1997.v113.pm9322516. [DOI] [PubMed] [Google Scholar]

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