Home LiteratureArticle Details
PMID: 9462212 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cytokine mRNA expression in intestinal tissue of interleukin-2 deficient mice with bowel inflammation.

Gut ·Vol. 41 ·No. 6 ·1997-12-00 ·Pages 793-800

Autenrieth IB, Bucheler N, Bohn E, Heinze G, Horak I

Abstract

Mice deficient in interleukin-2 (IL-2) develop inflammatory bowel disease resembling ulcerative colitis in humans. Recent studies provided evidence that alpha beta T cells, particularly CD4 T cells, rather than B cells, are involved in the pathogenesis of bowel inflammation of IL-2 deficient mice. To analyse the pattern of expression of cytokine mRNA in intestinal tissue of normal and IL-2 deficient mice. Expression of beta-actin, IL-1 alpha, IL-1 beta, IL-6, IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta 1 (TGF-beta 1) mRNA was analysed in colon and small intestinal tissue of both IL-2 deficient (IL-2-/-) mice and normal (wild type) litter mates (IL-2+/+) at different ages by using qualitative, as well as semiquantitative, competitive reverse transcription polymerase chain reaction (RT-PCR). Results were correlated with the phase of progression of the disease, as determined by histology. IL-2-/- mice had expressed low levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma mRNA in the colon by 1.5 weeks of age. In advance of the development of histologically and clinically detectable bowel inflammation, expression of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and IL-10, but not TGF-beta 1, mRNA increased in the colon of IL-2 deficient mice. In contrast, IL-2+/+ mice expressed TGF-beta 1 mRNA in colon tissue at 13 and 23 weeks of age, but not IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IL-10, or IFN-gamma mRNA. Levels of expression of cytokine mRNA in tissue from the small intestine were comparable in IL-2-/- and IL-2+/+ mice. Bowel inflammation in IL-2 deficient mice is preceded by an increase in IL-1 alpha, IL-1 beta, TNF-alpha, and IFN-gamma mRNA expression in colon tissue. Low levels of TGF-beta 1, but high levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and IL-10 mRNA expression correlate with the manifestation of severe colitis, and suggest that T cells and macrophages are involved in bowel inflammation of IL-2 deficient mice.

MeSH Terms
Actins/genetics Animals Colon/immunology Cytokines/genetics,metabolism Gene Expression Inflammatory Bowel Diseases/immunology,metabolism Interferon-gamma/genetics Interleukin-1/genetics Interleukin-10/genetics Interleukin-2/deficiency Interleukin-6/genetics Intestinal Mucosa/metabolism Intestine, Small/immunology Intestines/immunology Mice Mice, Inbred C57BL Mice, Mutant Strains Polymerase Chain Reaction RNA, Messenger/analysis,metabolism Transforming Growth Factor beta/genetics Tumor Necrosis Factor-alpha/genetics
Chemicals
Actins Cytokines Interleukin-1 Interleukin-2 Interleukin-6 RNA, Messenger Transforming Growth Factor beta Tumor Necrosis Factor-alpha Interleukin-10 Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Autenrieth I B
Max v. Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität, München, Germany.
Bucheler N
Bohn E
Heinze G
Horak I
References (54)
54 references, click to expand
  1. Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis.
    Gastroenterology. 1992 May;102(5):1620-7 PMID: 1568572
  2. Induction and prevention of colonic inflammation in IL-2-deficient mice.
    J Immunol. 1997 Jan 15;158(2):566-73 PMID: 8992969
  3. Kinetic analysis of cytokine gene expression in the livers of naive and immune mice infected with Listeria monocytogenes. The immediate early phase in innate resistance and acquired immunity.
    J Immunol. 1992 Nov 1;149(9):3016-22 PMID: 1401926
  4. Interleukin-2.
    Curr Opin Immunol. 1992 Jun;4(3):271-6 PMID: 1418705
  5. Tumor necrosis factor-alpha gene expression in the tissues of normal mice.
    Cytokine. 1992 Sep;4(5):340-6 PMID: 1420994
  6. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.
    Nature. 1992 Oct 22;359(6397):693-9 PMID: 1436033
  7. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.
    Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 PMID: 8421714
  8. Cytokine mRNA expression in intestine from normal and inflammatory bowel disease patients.
    Clin Immunol Immunopathol. 1993 Jan;66(1):52-8 PMID: 8440073
  9. Immunohistological characterization of the cellular immune response against Yersinia enterocolitica in mice: evidence for the involvement of T lymphocytes.
    Immunobiology. 1993 Jan;187(1-2):1-16 PMID: 8505058
  10. Functional interleukin-2 receptors on intestinal epithelial cells.
    J Clin Invest. 1993 Jul;92(1):527-32 PMID: 8326018
  11. Chronic intestinal inflammation: an unexpected outcome in cytokine or T cell receptor mutant mice.
    Cell. 1993 Oct 22;75(2):203-5 PMID: 8402907
  12. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene.
    Cell. 1993 Oct 22;75(2):253-61 PMID: 8402910
  13. Interleukin-10-deficient mice develop chronic enterocolitis.
    Cell. 1993 Oct 22;75(2):263-74 PMID: 8402911
  14. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.
    Cell. 1993 Oct 22;75(2):274-82 PMID: 8104709
  15. T-cell activation in human intestinal mucosa: the role of superantigens.
    Gastroenterology. 1993 Nov;105(5):1421-30 PMID: 8224645
  16. Immune responses in interleukin-2-deficient mice.
    Science. 1993 Nov 12;262(5136):1059-61 PMID: 8235625
  17. Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist.
    Gastroenterology. 1994 Mar;106(3):637-42 PMID: 8119534
  18. [Effect of interleukin 2 on the proliferation of two intestinal cell lines and on the expression of TGF-beta gene and JUN/FOS oncogenes].
    Gastroenterol Clin Biol. 1993;17(12):925-31 PMID: 8125225
  19. Tissue interleukin 1 and interleukin-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats.
    Gastroenterology. 1994 Apr;106(4):960-72 PMID: 8144001
  20. Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease.
    Gastroenterology. 1994 Jun;106(6):1455-66 PMID: 8194690
  21. Early gamma interferon mRNA expression is associated with resistance of mice against Yersinia enterocolitica.
    Infect Immun. 1994 Jul;62(7):3027-32 PMID: 8005693
  22. Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4.
    Eur J Immunol. 1994 Jan;24(1):281-4 PMID: 7517363
  23. Gastrointestinal inflammation. Inflammatory bowel disease in knockout mice.
    Curr Biol. 1994 Mar 1;4(3):261-3 PMID: 7922332
  24. Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice.
    Gastroenterology. 1994 Dec;107(6):1643-52 PMID: 7958674
  25. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats.
    J Exp Med. 1994 Dec 1;180(6):2359-64 PMID: 7964509
  26. Impaired response of activated mononuclear phagocytes to interleukin 4 in inflammatory bowel disease.
    Gastroenterology. 1995 Jan;108(1):21-33 PMID: 7806044
  27. Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa.
    Gastroenterology. 1995 Jan;108(1):40-50 PMID: 7806062
  28. Cytokines in Crohn's colitis.
    Am J Surg. 1995 Jan;169(1):133-6 PMID: 7817982
  29. 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):2434-40 PMID: 7868909
  30. Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease.
    Gastroenterology. 1995 May;108(5):1434-44 PMID: 7729636
  31. Alterations of the immune system in ulcerative colitis and Crohn's disease.
    Adv Immunol. 1988;42:285-328 PMID: 3284291
  32. Crohn's disease and the mycobacterioses: a review and comparison of two disease entities.
    Clin Microbiol Rev. 1989 Jan;2(1):90-117 PMID: 2644025
  33. Tumor necrosis factor mRNA localized to Paneth cells of normal murine intestinal epithelium by in situ hybridization.
    J Exp Med. 1990 Jan 1;171(1):327-32 PMID: 2404082
  34. Inflammatory bowel disease (1)
    N Engl J Med. 1991 Sep 26;325(13):928-37 PMID: 1881418
  35. Inflammatory bowel disease (2)
    N Engl J Med. 1991 Oct 3;325(14):1008-16 PMID: 1886623
  36. Loss of interleukin-2-producing intestinal CD4+ T cells in inflammatory bowel disease.
    Gastroenterology. 1991 Dec;101(6):1594-605 PMID: 1683326
  37. Mycobacterial diseases of the gut: some impact from molecular biology.
    Gut. 1992 Feb;33(2):145-7 PMID: 1541405
  38. Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells.
    Immunity. 1994 Oct;1(7):553-62 PMID: 7600284
  39. Severe colitis in mice with aberrant thymic selection.
    Immunity. 1995 Jul;3(1):27-38 PMID: 7621076
  40. Adequacy of mucosal biopsies for evaluation of intestinal cytokine-specific mRNA. Comparative study of RT-PCR in biopsies and isolated cells from normal and inflamed intestine.
    Dig Dis Sci. 1995 Jul;40(7):1498-505 PMID: 7543040
  41. T cells in inflammatory bowel disease: protective and pathogenic roles.
    Immunity. 1995 Aug;3(2):171-4 PMID: 7648390
  42. Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice.
    Nat Genet. 1995 Jun;10(2):143-50 PMID: 7663509
  43. Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin-2-deficient colitis.
    Eur J Immunol. 1995 Sep;25(9):2618-25 PMID: 7589135
  44. Antibodies to interleukin 12 abrogate established experimental colitis in mice.
    J Exp Med. 1995 Nov 1;182(5):1281-90 PMID: 7595199
  45. T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice.
    J Exp Med. 1995 Nov 1;182(5):1567-72 PMID: 7595226
  46. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin.
    Science. 1995 Nov 17;270(5239):1203-7 PMID: 7502046
  47. Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells.
    Eur J Immunol. 1995 Nov;25(11):3053-9 PMID: 7489743
  48. IL-12 is essential for resistance against Yersinia enterocolitica by triggering IFN-gamma production in NK cells and CD4+ T cells.
    J Immunol. 1996 Feb 15;156(4):1458-68 PMID: 8568248
  49. Inflammatory bowel disease.
    N Engl J Med. 1996 Mar 28;334(13):841-8 PMID: 8596552
  50. Gi2 alpha protein deficiency: a model of inflammatory bowel disease.
    J Clin Immunol. 1995 Nov;15(6 Suppl):101S-105S PMID: 8613481
  51. Penetration of M cells and destruction of Peyer's patches by Yersinia enterocolitica: an ultrastructural and histological study.
    J Med Microbiol. 1996 Apr;44(4):285-94 PMID: 8606357
  52. Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance.
    J Exp Med. 1996 Jun 1;183(6):2605-16 PMID: 8676081
  53. A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.
    J Exp Med. 1996 Jun 1;183(6):2669-74 PMID: 8676088
  54. Analysis of cytokine mRNA levels in interleukin-4-transgenic mice by quantitative polymerase chain reaction.
    Eur J Immunol. 1992 May;22(5):1179-84 PMID: 1533590
Article Info
Journal
Gut
Abbr.
Gut
ISSN
0017-5749
Published
1997-12-00
Pages
793-800
Language
English
Region
England
NLM ID
2985108R
PMCID
PMC1891612
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]