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Gut. Aug 1999; 45(2): 246–251.
PMCID: PMC1727615

Interleukin 1 and interleukin 1β converting enzyme (caspase 1) expression in the human colonic epithelial barrier. Caspase 1 downregulation in colon cancer

Abstract

BACKGROUND—Interleukin (IL) 1β converting enzyme (now known as caspase 1) is able to process pro-IL-1β into its active form and is involved in proapoptotic signalling.
AIMS—To characterise IL-1 and caspase 1 expression in human colonic epithelial cells.
METHODS—Intracellular IL-1 content (IL-1α and IL-1β) was measured by ELISA in freshly isolated human normal colonocytes. Caspase 1 expression was determined both at the mRNA level using in situ hybridisation and reverse transcription polymerase chain reaction, and at the protein level by immunoblotting experiments using antibodies specific for the proform of caspase 1 and for its cleavage forms.
RESULTS—Low amounts of IL-1β were found in nearly all preparations (92%), and IL-1α was detected in only 45% of human colonocyte preparations. The normal colonic epithelium strongly expressed caspase 1, both at the mRNA level and at the protein level in its latent form. In contrast, caspase 1 was not expressed in colon cancer (primary colonic adenocarcinomas and cancer cell lines).
CONCLUSIONS—The demonstration that the human colonic epithelial barrier is able to express caspase 1 and its substrate IL-1β reinforces the concept that, under certain conditions, the epithelium could trigger an inflammatory reaction. In addition, the finding that caspase 1 was downregulated in colonic adenocarcinomas supports the concept that disrupted apoptosis pathways may be involved in tumour formation and/or may confer resistance to treatment.


Keywords: caspase 1; colonic epithelial cells; colon cancer; interleukin 1; interleukin 1β converting enzyme

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Selected References

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  • Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992 Apr 30;356(6372):768–774. [PubMed]
  • Nicholson DW, Thornberry NA. Caspases: killer proteases. Trends Biochem Sci. 1997 Aug;22(8):299–306. [PubMed]
  • Kumar S. ICE-like proteases in apoptosis. Trends Biochem Sci. 1995 May;20(5):198–202. [PubMed]
  • Cohen GM. Caspases: the executioners of apoptosis. Biochem J. 1997 Aug 15;326(Pt 1):1–16. [PMC free article] [PubMed]
  • Zepter K, Häffner A, Soohoo LF, De Luca D, Tang HP, Fisher P, Chavinson J, Elmets CA. Induction of biologically active IL-1 beta-converting enzyme and mature IL-1 beta in human keratinocytes by inflammatory and immunologic stimuli. J Immunol. 1997 Dec 15;159(12):6203–6208. [PubMed]
  • Branka JE, Vallette G, Jarry A, Bou-Hanna C, Lemarre P, Van PN, Laboisse CL. Early functional effects of Clostridium difficile toxin A on human colonocytes. Gastroenterology. 1997 Jun;112(6):1887–1894. [PubMed]
  • Vallette G, Jarry A, Lemarre P, Branka JE, Laboisse CL. NO-dependent and NO-independent IL-1 production by a human colonic epithelial cell line under inflammatory stress. Br J Pharmacol. 1997 May;121(2):187–192. [PMC free article] [PubMed]
  • McAlindon ME, Hawkey CJ, Mahida YR. Expression of interleukin 1 beta and interleukin 1 beta converting enzyme by intestinal macrophages in health and inflammatory bowel disease. Gut. 1998 Feb;42(2):214–219. [PMC free article] [PubMed]
  • Taylor CM, Blanchard B, Zava DT. A simple method to determine whole cell uptake of radiolabelled oestrogen and progesterone and their subcellular localization in breast cancer cell lines in monolayer culture. J Steroid Biochem. 1984 May;20(5):1083–1088. [PubMed]
  • Alnemri ES, Fernandes-Alnemri T, Litwack G. Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. J Biol Chem. 1995 Mar 3;270(9):4312–4317. [PubMed]
  • Hannon K, Johnstone E, Craft LS, Little SP, Smith CK, 2nd, Heiman ML, Santerre RF. Synthesis of PCR-derived, single-stranded DNA probes suitable for in situ hybridization. Anal Biochem. 1993 Aug 1;212(2):421–427. [PubMed]
  • Miossec C, Decoen MC, Durand L, Fassy F, Diu-Hercend A. Use of monoclonal antibodies to study interleukin-1 beta-converting enzyme expression: only precursor forms are detected in interleukin-1 beta-secreting cells. Eur J Immunol. 1996 May;26(5):1032–1042. [PubMed]
  • Ayala JM, Yamin TT, Egger LA, Chin J, Kostura MJ, Miller DK. IL-1 beta-converting enzyme is present in monocytic cells as an inactive 45-kDa precursor. J Immunol. 1994 Sep 15;153(6):2592–2599. [PubMed]
  • Casini-Raggi V, Kam L, Chong YJ, Fiocchi C, Pizarro TT, Cominelli F. Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. J Immunol. 1995 Mar 1;154(5):2434–2440. [PubMed]
  • Lammers KM, Jansen J, Bijlsma PB, Ceska M, Tytgat GN, Laboisse CL, van Deventer SJ. Polarised interleukin 8 secretion by HT 29/19A cells. Gut. 1994 Mar;35(3):338–342. [PMC free article] [PubMed]
  • Hoang P, Crotty B, Dalton HR, Jewell DP. Epithelial cells bearing class II molecules stimulate allogeneic human colonic intraepithelial lymphocytes. Gut. 1992 Aug;33(8):1089–1093. [PMC free article] [PubMed]
  • Radema SA, van Deventer SJ, Cerami A. Interleukin 1 beta is expressed predominantly by enterocytes in experimental colitis. Gastroenterology. 1991 May;100(5 Pt 1):1180–1186. [PubMed]
  • Boudreau N, Sympson CJ, Werb Z, Bissell MJ. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science. 1995 Feb 10;267(5199):891–893. [PMC free article] [PubMed]
  • Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, Matsuyama T, Mak TW, Taki S, Taniguchi T. An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. Nature. 1995 Aug 17;376(6541):596–599. [PubMed]
  • Stadnyk AW, Sisson GR, Waterhouse CC. IL-1 alpha is constitutively expressed in the rat intestinal epithelial cell line IEC-6. Exp Cell Res. 1995 Oct;220(2):298–303. [PubMed]
  • Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995 Mar 10;267(5203):1456–1462. [PubMed]
  • Los M, Herr I, Friesen C, Fulda S, Schulze-Osthoff K, Debatin KM. Cross-resistance of CD95- and drug-induced apoptosis as a consequence of deficient activation of caspases (ICE/Ced-3 proteases). Blood. 1997 Oct 15;90(8):3118–3129. [PubMed]

Figures and Tables

Figure 1
Intracellular IL-1 concentrations in isolated human colonocytes (n=49). Means are shown by horizontal bars and standard errors by vertical bars.
Figure 2
Detection of caspase 1 by in situ hybridisation in the normal human colonic mucosa. Colonocytes strongly expressed caspase 1 mRNA (A,B). Control section hybridised with a caspase 1 sense probe revealed no specific signal (C). ...
Figure 3
RT-PCR analysis of caspase 1 expression in human normal isolated colonocytes. Lane 1 shows DNA weight marker ϕX174-HaeIII. Lanes 2, 4, 6 show caspase 1 amplification products from three different ...
Figure 4
Caspase 1 expression in human normal isolated colonocytes at the protein level. Eight different cell lysates were subjected to immunoblotting experiments. They were run on SDS-PAGE gels, blotted, and probed with either an anticaspase 1 p45 ...
Figure 5
Downregulation of caspase 1 expression in colon cancer. (A) In situ hybridisation performed on cryostat sections of a primary colon adenocarcinoma shows that tumour cells (T) do not express caspase 1 mRNA, whereas normal crypts (N) in ...

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