Inhibitory Effect of IL-1ß on Galactose Intestinal Absorption in Rabbits

Abstract

Background/Aims: Recent studies from our laboratory have shown that nitric oxide is involved in the IL-1β-induced inhibition of D-fructose intestinal transport in rabbits. The aim of this work was to further the studies of IL-1β effect on D-galactose absorption in a septic state induced by intravenous administration of this cytokine. Methods: Galactose intestinal absorption was assessed employing three techniques: sugar uptake in jejunum everted rings, transepithelial flux in Ussing-type chambers and uptake assays in brush border membrane vesicles. The level of the Na⁺/D-glucose cotransporter (SGLT1) expression was analyzed by Western blot. Results: In sepsis condition the body temperature was increased and studies on cellular intestinal integrity have not shown modifications in the brush border membrane. However, D-galactose absorption across mucosa of jejunum was diminished in IL-1β treated rabbits. The levels of SGLT-1 were no significantly different in both animal groups (control and IL-1β treated), indicating that the cytokine could induce a reduction in the SGLT-1 functionality. The inhibition was significantly reversed by the activation of several PKC, PKA, MAPKs and nuclear factor (NF)-ĸB inhibitors administered 15 min before the IL-1β. Conclusion: The inhibitory effect of IL-1β on D-galactose absorption across mucosal side of enterocyte could be mediated by the activation of several kinases and nuclear factor (NF)-ĸB.

Involvement of Intracellular Signaling in the IL‐1β Inhibitory Effect on Fructose Intestinal Absorption

“…In addition, MG 132 has not effect “per se” in fructose absorption (data not shown). The results agree with previous studies carried out in our laboratory in relation to galactose intestinal absorption (Viñuales et al, ).…”

“…The possible involvement of the proteasome was also evaluated, on intestinal tissue and BBMV, using the potent cell‐permeable proteasome inhibitor MG 132 administered iv at 250 μg/kg bw 15 min before IL‐1β treatment (García‐Herrera et al, ; Viñuales et al, ). The results showed that MG 132 completely suppressed the inhibitory effect of Il‐1β on D ‐fructose intestinal transport (Fig.…”

“…We initially measured the effect of selective inhibitors of protein kinase C (PKC) and PKA with GF 109203X (500 ng/kg bw) and IP20 (0.155 mg/kg bw), respectively (Viñuales et al, ), on IL‐1β (0.2 μg/kg bw) effect in 5 mM D ‐fructose intestinal absorption. PKC inhibitor reversed completely the IL‐1β effect on sugar uptake but PKA inhibitor had a small effect (Fig.…”

“…Furthermore, studies by Al‐Sadi et al (, 2008, 2011, 2012) show that the IL‐1β‐induced increase in Caco‐2 monolayer tight junction (TJ) permeability is mediated by activation of extracellular signal‐regulated kinases ½ (ERK1/2) and a NF‐kB signalling pathway. In addition, we have found an inhibitory effect of this cytokine on D ‐galactose intestinal absorption by the activation of several kinases and NF‐kB (Viñuales et al, , ).…”

Regulation of ion channels and transporters by AMP-activated kinase (AMPK)

“…158 Among the carriers upregulated by NF-κB is the Na + /H + exchanger NHE3, 159 carriers downregulated by NF-κB include SGLT1. 160 NF-κB presumably regulates the expression of multiple further transport proteins and/or several signaling cascades involved in transport regulation. For instance, NF-κB downregulates the expression of the serum and glucocorticoid inducible kinase SGK1, 158 a powerful regulator of a wide variety of channels, carriers and Na + /K + ATPase.…”