Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells

Hitoshi Ogawa, David G. Binion, Jan Heidemann, Monica Theriot, Pamela J. Fisher, Nathan A. Johnson, Mary F. Otterson, Parvaneh Rafiee

    Research output: Contribution to journalArticlepeer-review

    37 Citations (Scopus)

    Abstract

    Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a homing receptor preferentially expressed on gut-associated endothelial cells that plays a central role in leukocyte traffic into the mucosal immune compartment. Although the molecular mechanisms underlying endothelial ICAM-1 or E-selectin expression have been intensively investigated, the mechanisms that regulate human MAdCAM-1 expression have not been defined. We report MAdCAM-1 gene and protein expression in primary cultures of human intestinal microvascular endothelial cells (HIMEC) that was not demonstrated in human umbilical vein endothelial cells. Similar to ICAM-1 and E-selectin expression, MAdCAM-1 gene expression in HIMEC was inducible with TNF-α, IL-1β, or LPS activation. However, in striking contrast to ICAM-1 and E-selectin expression, MAdCAM-1 mRNA and protein expression in HIMEC was heavily dependent on culture duration and/or cellular, density, suggesting a prominent role for cell-cell interaction among these endothelial cells in the expression of the mucosal addressin. MAdCAM-1 expression was inhibited by both SN-50 (NF-κB inhibitor) and LY-294002 [phosphatidylinositol 3-kinase (PI3-K) inhibitor], whereas ICAM-1 and E-selectin expression was inhibited by SN-50 but not by LY-294002. The Akt phosphorylation by TNF-α or LPS was greater at higher cell density, demonstrating a pattern similar to that of MAdCAM-1 expression. NF-κB activation was not affected by cellular density in HIMEC. MAdCAM-1 expression in human gut endothelial cells is regulated by distinct signaling mechanisms involving both NF-κB and PI3-K/Akt. These data also suggest that PI3-K/ Akt is involved in the gut-specific differentiation of HIMEC, which results in expression of the mucosal addressin MAdCAM-1.

    Original languageEnglish
    JournalAmerican Journal of Physiology - Cell Physiology
    Volume288
    Issue number2 57-2
    DOIs
    Publication statusPublished - 2005 Feb

    Keywords

    • Cell adhesion molecules
    • Nuclear factor-κB
    • Phosphatidylinositol 3-kinase

    ASJC Scopus subject areas

    • Clinical Biochemistry
    • Cell Biology
    • Physiology

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