Interferon-γ and interleukin-10 reciprocally regulate endothelial junction integrity and barrier function

Tadayuki Oshima, F. Stephen Laroux, Laura L. Coe, Zenichi Morise, Shigeyuki Kawachi, Philippe Bauer, Matthew B. Grisham, Robert D. Specian, Patsy Carter, Stephen Jennings, D. Neil Granger, Takashi Joh, J. Steven Alexander

Research output: Contribution to journalArticlepeer-review

124 Citations (Scopus)

Abstract

Inflammatory bowel disease (IBD) is associated with Th1/Th2 cytokine dysregulation, leukocyte extravasation, and tissue edema, but the mechanisms for cytokine-mediated vascular dysfunction are not understood. To investigate how cytokines might control edema in IBD, we determined vascular permeability and IFN-γ expression in two models of murine colitis: SCID mice reconstituted with CD45RBhigh T-lymphocytes (CD45RBhigh/SCID mice), and interleukin-10 gene deficient (IL-10-/-) mice. We also investigated the in vitro effects of IFN-γ and IL-10 on human endothelial solute barrier and junction protein expression. Vascular permeability in CD45RBhigh/SCID and IL-10-/- mice was quantified using tissue 131I-IgG accumulation. The IFN-γ message was quantified using the ribonuclease protection assay. Endothelial barrier integrity in vitro was measured by transmonolayer electrical resistance, and junctional proteins were examined by immunoblotting and fluorescence microscopy. Both CD45RBhigh/SCID and IL-10-/- mice exhibit enhanced colonic microvascular leakage and IFN-γ message levels compared to their respective controls. In vitro, IFN-γ also reduced endothelial barrier (monolayer electrical resistance, increased albumin permeability) and reduced tight junction (occludin) expression and staining. These effects were reversed by pretreatment of monolayers with IL-10. Therefore, in vivo IFN-γ and IL-10 may modulate microvascular leakage in IBD partly by controlling the expression of intestinal endothelial tight junctional proteins.

Original languageEnglish
Pages (from-to)130-143
Number of pages14
JournalMicrovascular Research
Volume61
Issue number1
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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