title: Interferon gamma bound to extracellular matrix changes the hyporesponsiveness to LPS in crypt but not villous intestinal epithelial cells.
abstract: Intestinal epithelial cells (IEC) are hyporesponsive to LPS. Responsiveness to luminal bacteria has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). In support of this, previous studies have demonstrated that some intestinal epithelial cell lines are induced by IFN-gamma to respond to LPS. However, both the responsiveness to LPS and the effect of IFN-gamma in intestinal cell lines are heterogeneous. In addition, IFN-gamma may be sequestered in the extracellular matrix (ECM) compartment. The ECM-bound form is more effective than soluble IFN-gamma in producing its biological effects in several experimental models. We investigated the effect of ECM-bound and soluble IFN-gamma treatment on interleukin-8 (IL-8) secretion in response to LPS in freshly isolated villous and crypt cells. We demonstrate that ECM-bound, but not soluble IFN-gamma, induced an increase in IL-8 secretion in response to LPS in undifferentiated crypt cells. This effect was associated with an increase in TLR4 expression. In contrast, mature villous cells did not modify their response to LPS when treated with IFN-gamma (ECM-bound or soluble). These results suggest that selective changes in immature crypt cells induced by IFN-gamma bound to extracellular matrix could contribute to inappropriate responsiveness to commensal bacteria in IBD.
authors.affiliation: Laboratorio de Fisiología Gastrointestinal, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
authors.forename: Jansi
authors.initials: J
authors.lastname: Alvarado
authors.forename: Peter
authors.initials: P
authors.lastname: Taylor
authors.forename: Jesús R Del
authors.initials: JR
authors.lastname: Castillo
authors.forename: Luz E
authors.initials: LE
authors.lastname: Thomas
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006967:Hypersensitivity; D007371:Interferon-gamma / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D013552:Swine; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D007371:Interferon-gamma