IL-1 Beta -converting Enzyme (caspase-1) in Intestinal Inflammation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Oct 19

PMID 11606779

Citations 200

Authors

B Siegmund

H A Lehr

G Fantuzzi

C A Dinarello

Affiliations

Soon will be listed here.

Abstract

IL-1 beta-converting enzyme (ICE; caspase-1) is the intracellular protease that cleaves the precursors of IL-1 beta and IL-18 into active cytokines. In the present study, the effect of ICE deficiency was evaluated during experimental colitis in mice. In acute dextran sulfate sodium-induced colitis, ICE-deficient (ICE KO) mice exhibited a greater than 50% decrease of the clinical scores weight loss, diarrhea, rectal bleeding, and colon length, whereas daily treatment with IL-1 receptor antagonist revealed a modest reduction in colitis severity. To further characterize the function of ICE and its role in intestinal inflammation, chronic colitis was induced over a 30-day time period. During this chronic time course, ICE KO mice exhibited a near complete protection, as reflected by significantly reduced clinical scores and almost absent histological signs of colitis. Consistently, colon shortening occurred only in dextran sulfate sodium-exposed wild-type mice but not in ICE KO mice. Protection was accompanied by reduced spontaneous release of the proinflammatory cytokines IL-18, IL-1 beta, and IFN-gamma from total colon cultures. In addition, flow cytometric analysis of isolated mesenteric lymph node cells revealed evidence of reduced cell activation in ICE KO mice as evaluated by surface expression of CD3 CD69 and CD4 CD25. We conclude that inhibition of ICE represents a novel anti-inflammatory strategy for intestinal inflammation.

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References

Puren A, Razeghi P, Fantuzzi G, Dinarello C . Interleukin-18 enhances lipopolysaccharide-induced interferon-gamma production in human whole blood cultures. J Infect Dis. 1998; 178(6):1830-4. DOI: 10.1086/314481. View

Watson R, Rotstein O, Parodo J, Bitar R, Marshall J, William R . The IL-1 beta-converting enzyme (caspase-1) inhibits apoptosis of inflammatory neutrophils through activation of IL-1 beta. J Immunol. 1998; 161(2):957-62. View

Fantuzzi G, Dinarello C . Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1). J Clin Immunol. 1999; 19(1):1-11. DOI: 10.1023/a:1020506300324. View

Coeshott C, Ohnemus C, Pilyavskaya A, Ross S, Wieczorek M, Kroona H . Converting enzyme-independent release of tumor necrosis factor alpha and IL-1beta from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. Proc Natl Acad Sci U S A. 1999; 96(11):6261-6. PMC: 26869. DOI: 10.1073/pnas.96.11.6261. View

Pizarro T, Michie M, Bentz M, Woraratanadharm J, Smith Jr M, Foley E . IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells. J Immunol. 1999; 162(11):6829-35. View

Monteleone G, Trapasso F, Parrello T, Biancone L, Stella A, Iuliano R . Bioactive IL-18 expression is up-regulated in Crohn's disease. J Immunol. 1999; 163(1):143-7. View

Marzio R, Mauel J . CD69 and regulation of the immune function. Immunopharmacol Immunotoxicol. 1999; 21(3):565-82. DOI: 10.3109/08923979909007126. View

Fuss I, Marth T, Neurath M, Pearlstein G, Jain A, Strober W . Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. Gastroenterology. 1999; 117(5):1078-88. DOI: 10.1016/s0016-5085(99)70392-6. View

Nicklin M, Hughes D, Barton J, Ure J, Duff G . Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J Exp Med. 2000; 191(2):303-12. PMC: 2195758. DOI: 10.1084/jem.191.2.303. View

10.

Horai R, Saijo S, Tanioka H, Nakae S, Sudo K, Okahara A . Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J Exp Med. 2000; 191(2):313-20. PMC: 2195765. DOI: 10.1084/jem.191.2.313. View

11.

Fantuzzi G, Mendoza L, Fuentes A, Anasagasti M, Martin J, Carrascal T . IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proc Natl Acad Sci U S A. 2000; 97(2):734-9. PMC: 15399. DOI: 10.1073/pnas.97.2.734. View

12.

Faggioni R, Jones-Carson J, Reed D, Dinarello C, Feingold K, Grunfeld C . Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor alpha and IL-18. Proc Natl Acad Sci U S A. 2000; 97(5):2367-72. PMC: 15807. DOI: 10.1073/pnas.040561297. View

13.

Mahida Y . The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis. 2000; 6(1):21-33. DOI: 10.1097/00054725-200002000-00004. View

14.

Atreya R, Mudter J, Finotto S, Mullberg J, Jostock T, Wirtz S . 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; 6(5):583-8. DOI: 10.1038/75068. View

15.

Saubermann L, Beck P, de Jong Y, Pitman R, Ryan M, Kim H . Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice. Gastroenterology. 2000; 119(1):119-28. DOI: 10.1053/gast.2000.9114. View

16.

Read S, Malmstrom V, Powrie F . Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med. 2000; 192(2):295-302. PMC: 2193261. DOI: 10.1084/jem.192.2.295. View

17.

Zhang Z, Wang L, Seydel K, Li E, Ankri S, Mirelman D . Entamoeba histolytica cysteine proteinases with interleukin-1 beta converting enzyme (ICE) activity cause intestinal inflammation and tissue damage in amoebiasis. Mol Microbiol. 2000; 37(3):542-8. DOI: 10.1046/j.1365-2958.2000.02037.x. View

18.

Joosten L, van De Loo F, Lubberts E, Helsen M, Netea M, van der Meer J . An IFN-gamma-independent proinflammatory role of IL-18 in murine streptococcal cell wall arthritis. J Immunol. 2000; 165(11):6553-8. DOI: 10.4049/jimmunol.165.11.6553. View

19.

Siegmund B, Rieder F, Albrich S, Wolf K, Bidlingmaier C, Firestein G . Adenosine kinase inhibitor GP515 improves experimental colitis in mice. J Pharmacol Exp Ther. 2000; 296(1):99-105. View

20.

Kucharzik T, Lugering N, Rautenberg K, Lugering A, Schmidt M, Stoll R . Role of M cells in intestinal barrier function. Ann N Y Acad Sci. 2001; 915:171-83. DOI: 10.1111/j.1749-6632.2000.tb05240.x. View