TNF-α induces vectorial secretion of IL-8 in Caco-2 cells.
BACKGROUND
Intestinal epithelial cells represent an important component of innate immunity, with sophisticated responses to inflammatory stimuli. The manner in which intestinal epithelial cell polarity affects responses to inflammatory stimuli is largely unknown. We hypothesized that polarized intestinal epithelial cells exhibit a bidirectional inflammatory response dependent upon the location of the stimulus.


METHODS
Caco-2 cells were grown on semi-permeable inserts in a dual-compartment culture system and treated with tumor necrosis factor-α (TNF-α; 100 ng/ml) or serum-free media in the apical or basolateral chamber. Interleukin-8 (IL-8) production in each chamber was measured by enzyme-linked immunosorbent assay. To determine receptor specificity, anti-TNF receptor antibodies were added to the apical or basolateral chamber.


RESULTS
Basolateral stimulation with TNF-α resulted in increased apical and basolateral IL-8 production. Apical TNF-α stimulation resulted in increased apical, but not basolateral IL-8 production. Receptor blockade suggested TNF receptor 1 involvement on both apical and basolateral membranes, while TNF receptor 2 was only active on the apical membrane.


CONCLUSIONS
Polarized intestinal epithelial cells respond to TNF-α stimulation with focused, directional secretion of the proinflammatory cytokine IL-8. These findings are important because they suggest that intestinal epithelial cells are capable of organizing their response to inflammatory signals and producing inflammatory mediators in a bidirectional, vectorial fashion.
Sonnier
Dennis I
DI
Department of Surgery, University of Cincinnati College of Medicine, Mail Location 0558, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. sonnieds@ucmail.uc.edu
Bailey
Stephanie R
SR
Schuster
Rebecca M
RM
Lentsch
Alex B
AB
Pritts
Timothy A
TA
D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha
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