TY - JOUR
T1 - Interferon-γ and interleukin-10 reciprocally regulate endothelial junction integrity and barrier function
AU - Oshima, Tadayuki
AU - Laroux, F. Stephen
AU - Coe, Laura L.
AU - Morise, Zenichi
AU - Kawachi, Shigeyuki
AU - Bauer, Philippe
AU - Grisham, Matthew B.
AU - Specian, Robert D.
AU - Carter, Patsy
AU - Jennings, Stephen
AU - Granger, D. Neil
AU - Joh, Takashi
AU - Alexander, J. Steven
N1 - Funding Information:
This work was supported by National Institutes of Health Grants HL47615, DK43785, and DK4766 and by The Feist Foundation of LSU Health Sciences Center in Shreveport.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1006/mvre.2000.2288
DO - 10.1006/mvre.2000.2288
M3 - Article
C2 - 11162203
AN - SCOPUS:0034757324
SN - 0026-2862
VL - 61
SP - 130
EP - 143
JO - Microvascular Research
JF - Microvascular Research
IS - 1
ER -
