AJP - Cell Physiology, Vol 267, Issue 2 C537-C543, Copyright © 1994 by American Physiological Society
Modulation of growth factor and cytokine-induced increases in T84 cell monolayer permeability by media components
J. A. McRoberts and N. E. Riley
Department of Medicine, Harbor-University of California, Los Angeles Medical Center, Torrance 90502.
Previous studies have shown that insulin, insulin-like growth factors, and
interferon-gamma cause an increase the paracellular permeability across T84
human colonic epithelial cell monolayers. The striking similarity in the
time course and the structural changes in the actin cytoskeleton prompted
us to test whether these factors influenced the paracellular permeability
by a common mechanism. T84 cell monolayers were grown in variously modified
media, and the effect of all three factors was tested by measuring the
conductance of monolayers mounted in Ussing chambers. Media additions or
deletions that modify cellular carbohydrate metabolism markedly influenced
the response to all these peptides. In particular, the increase in
conductance produced by each of the three peptides was 1) inhibited by
addition of short-chain fatty acids, principally n-butyrate and propionate;
2) attenuated by the replacement of media glucose with slowly metabolized
and nonmetabolized sugars; 3) potentiated by decreasing the media iron
concentration; and 4) inhibited by increasing the media iron concentration.
The effects of short-chain fatty acids, glucose, and iron were all shown to
be dose dependent. In addition, the ability of high media iron to prevent
the increase in permeability caused by all three factors was shown to
require ambient oxygen. Together, these results strongly suggest that
insulin, insulin-like growth factors, and interferon-gamma increase the
permeability across T84 cell monolayers through a common mechanism that is
modulated by glucose-derived metabolites and oxidative metabolism.
