The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor alpha mutant mice.

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  • Author(s): Mizoguchi A;Mizoguchi A; Mizoguchi E; Bhan AK
  • Source:
    Gastroenterology [Gastroenterology] 1999 Feb; Vol. 116 (2), pp. 320-6.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: W.B. Saunders Country of Publication: United States NLM ID: 0374630 Publication Model: Print Cited Medium: Print ISSN: 0016-5085 (Print) Linking ISSN: 00165085 NLM ISO Abbreviation: Gastroenterology Subsets: MEDLINE
    • Publication Information:
      Publication: Philadelphia, PA : W.B. Saunders
      Original Publication: Baltimore.
    • Subject Terms:
      Colitis/*metabolism ; Interferon-gamma/*metabolism ; Interleukin-4/*metabolism ; Receptors, Antigen, T-Cell, alpha-beta/*genetics; Animals ; Colitis/pathology ; Cytokines/metabolism ; Interferon-gamma/administration & dosage ; Interleukin-4/administration & dosage ; Lymph Nodes/metabolism ; Mesentery ; Mice ; Mutation ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction
    • Abstract:
      Background & Aims: T-cell receptor alpha mutant (TCRalpha-/-) mice spontaneously develop colitis resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-gamma in the pathogenesis of colitis was examined by creating IL-4- or IFN-gamma-deficient TCRalpha-/- mice.
      Methods: Double-mutant mice were created by crossing TCRalpha-/- mice with IL-4- or IFN-gamma-deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed.
      Results: The lack of IL-4 dramatically suppressed the development of colitis at 6 months of age. In contrast, IFN-gamma-/- x TCRalpha-/- mice developed colitis similar to that present in TCRalpha-/- mice. Furthermore, proliferation of colonic epithelial cells was markedly increased in TCRalpha-/- mice and IFN-gamma-/- x TCRalpha-/- mice compared with IL-4(-/-) x TCRalpha-/- mice. Continuous administration of recombinant IL-4 led to increased colonic epithelial cell proliferation in IL-4(-/-) x TCRalpha-/- mice.
      Conclusions: IL-4 plays an important role in the development of colitis in TCRalpha-/- mice. In contrast, severe colitis in TCRalpha-/- mice can develop in the absence of IFN-gamma.
    • Grant Information:
      DK43551 United States DK NIDDK NIH HHS; DK47677 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Cytokines)
      0 (Receptors, Antigen, T-Cell, alpha-beta)
      0 (Recombinant Proteins)
      207137-56-2 (Interleukin-4)
      82115-62-6 (Interferon-gamma)
    • Publication Date:
      Date Created: 19990129 Date Completed: 19990218 Latest Revision: 20220330
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/s0016-5085(99)70128-9
    • Accession Number:
      9922312