Transforming growth factor-β1 preserves epithelial barrier function: Identification of receptors, biochemical intermediates, and cytokine antagonists
✍ Scribed by Sarah Planchon; Claudio Fiocchi; Vivian Takafuji; James K. Roche
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 449 KB
- Volume
- 181
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
Freshly isolated human mucosal T lymphocytes in vitro can markedly diminish an important property of intestinal epithelium-its barrier function. On the other hand, cytokines and their cellular receptors, which maintain homeostasis of epithelia, limit epithelial permeability, and preserve barrier function, are not well characterized. Using a described human colonic epithelial cell monolayer system, we found that transforming growth factor-1 (TGF-1) preserved 75% or more of epithelial barrier function, quantitated electrophysiologically, even in the presence of cytokines generated by a high density of barrier-disruptive mucosaderived mononuclear cells. In opposing the TGF-1 effect, cytokines able to reduce barrier function were spontaneously secreted by mucosal T cells and were increased in their barrier effect after T-lymphocyte activation. Further, neutralization of individual cytokines with specific monoclonal antibodies abrogated the lymphocyte-induced reduction in epithelial barrier function, and identified interferon gamma (IFN-␥), interleukin (IL)-4, and IL-10, but not IL-6, as the primary cytokines whose barrier effects were curtailed by TGF-1. Receptors (RI and RII) for TGF-1 were found to be localized primarily to the apical and basal membranes of surface epithelium in colonic crypts. These findings provide the scientific basis for new strategies to pharmacologically enhance the barrier function of epithelia in mucosal organs regularly exposed to environmental antigens and to T-lymphocyte products.