title: Interleukin-1beta reduces galactose transport in intestinal epithelial cells in a NF-kB and protein kinase C-dependent manner.
abstract: Interleukins (IL), aside from their role in the regulation of the immune cascade, they have also been shown to modulate intestinal transport function. IL-1β is a potent inflammatory cytokine involved in many important cellular functions. The aim of this work was to study the in vitro effect of IL-1β on d-galactose transport across intestinal epithelia in rabbit jejunum and Caco-2 cells. The results showed that d-galactose intestinal absorption was diminished in IL-1β treated jejunum rabbits without affecting the Na(+), K(+)-ATPase activity. The presence of IL-1 cell-surface receptors was confirmed by addition to tissue of a specific IL-1 receptor antagonist (IL-1ra). The cytokine did not inhibit either the uptake of d-galactose nor modified the sodium-glucose transport (SGLT1) protein levels in the brush border membrane vesicles, suggesting an indirect IL effect. The IL-inhibition was significantly reversed in the presence of inhibitors of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs). The proteasome selective inhibitor completely abolished the IL-effect. Furthermore, the cytokine inhibition on galactose transport related to NF-kB activation was also confirmed in Caco-2 cells. In summary, the direct addition of IL-1β to intestinal epithelia inhibits d-galactose transport by a possible reduction in the SGLT1 activity. This event may be mediated by several transduction pathways activated during the inflammatory processes related to several protein kinases and nuclear factor, NF-kB. The IL-effect is independent of hormonal milieu and nervous stimuli.
authors.affiliation: Physiology Unit, Department of Pharmacology and Physiology, Veterinary Faculty, University of Zaragoza, E-50013 Zaragoza, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Viñuales
authors.forename: Sonia
authors.initials: S
authors.lastname: Gascón
authors.forename: Cristina
authors.initials: C
authors.lastname: Barranquero
authors.forename: Jesús
authors.initials: J
authors.lastname: Osada
authors.forename: Ma Jesús
authors.initials: MJ
authors.lastname: Rodríguez-Yoldi
mesh_terms: D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D051269:Sodium-Glucose Transporter 1 / Q000502:physiology
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D051269:Sodium-Glucose Transporter 1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005690:Galactose
keywords: Galactose; Gut; IL-1β; Kinases; NF-kB