Roles of Toll-Like Receptor 4, I[kappa]B Kinase, and the Proteasome in the Intestinal Alterations Caused by Sepsis

Background Lipopolysaccharide decreases intestinal contractility and induces the production of cytokines, which play an important role in the pathogenesis of sepsis. Aim The objective of the present study was to examine the role of Toll-like receptor 4, I[kappa]B kinase, and the proteasome in the in...

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Published in:Digestive diseases and sciences 2015-05, Vol.60 (5), p.1223
Main Authors: Gonzalo, Sergio, Valero, Marta Sofía, Martínez de Salinas, Fernando, Vergara, Claudia, Arruebo, María Pilar, Plaza, Miguel Ángel, Murillo, María Divina
Format: Article
Language:English
Subjects:
Interleukins
Neomycin
Peptides
RNA
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Summary:Background Lipopolysaccharide decreases intestinal contractility and induces the production of cytokines, which play an important role in the pathogenesis of sepsis. Aim The objective of the present study was to examine the role of Toll-like receptor 4, I[kappa]B kinase, and the proteasome in the intestinal alterations induced by lipopolysaccharide. Methods Sepsis was induced in rabbits by intravenous injection of lipopolysaccharide. Contractility studies of rabbit duodenum were performed in an organ bath. Expressions of interleukin-1[beta], interleukin-6, interleukin-8, interleukin-10, I[kappa]B kinase-[alpha], I[kappa]B kinase-[beta], I[kappa]B kinase-[gamma], and the proteasome mRNA were determined by RT-PCR on rabbit duodenum. Results Neomycin and polymyxin B (Toll-like receptor 4 inhibitors), IKK NBD peptide (I[kappa]B kinase complex inhibitor), and MG-132 (proteasome inhibitor) blocked partially the effects of lipopolysaccharide on the acetylcholine-, prostaglandin E.sub.2-, substance P-, and KCl-induced contractions in the longitudinal and circular smooth muscle of rabbit duodenum. Lipopolysaccharide increased the mRNA expression of interleukin-6 and interleukin-8 in duodenal tissue, and this effect was partly reversed by neomycin, polymyxin B, IKK NBD peptide, and MG-132. I[kappa]B kinase-[alpha], I[kappa]B kinase-[beta], I[kappa]B kinase-[gamma], and the proteasome mRNA expressions was not affected by lipopolysaccharide treatment. Conclusions Toll-like receptor 4, the I[kappa]B kinase complex, and the proteasome could be therapeutic targets in the treatment of sepsis symptoms in the intestine.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-014-3418-6