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, IκB 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-1β, interleukin-6, interleukin-8, interleukin-10, IκB kinase-α, IκB kinase-β, IκB kinase-γ, 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 (IκB kinase complex inhibitor), and MG-132 (proteasome inhibitor) blocked partially the effects of lipopolysaccharide on the acetylcholine-, prostaglandin E2-, 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. IκB kinase-α, IκB kinase-β, IκB kinase-γ, and the proteasome mRNA expressions was not affected by lipopolysaccharide treatment. CONCLUSIONS: Toll-like receptor 4, the IκB kinase complex, and the proteasome could be therapeutic targets in the treatment of sepsis symptoms in the intestine.
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, IκB 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-1β, interleukin-6, interleukin-8, interleukin-10, IκB kinase-α, IκB kinase-β, IκB kinase-γ, 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 (IκB kinase complex inhibitor), and MG-132 (proteasome inhibitor) blocked partially the effects of lipopolysaccharide on the acetylcholine-, prostaglandin E2-, 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. IκB kinase-α, IκB kinase-β, IκB kinase-γ, and the proteasome mRNA expressions was not affected by lipopolysaccharide treatment. CONCLUSIONS:Toll-like receptor 4, the IκB kinase complex, and the proteasome could be therapeutic targets in the treatment of sepsis symptoms in the intestine.
Authors: David C Swinney; Yi-Zheng Xu; Liliana E Scarafia; Ina Lee; Amy Y Mak; Qing-Fen Gan; Chakkodabylu S Ramesha; Mary A Mulkins; Jim Dunn; On-Yee So; Teresa Biegel; Marie Dinh; Pamela Volkel; Jim Barnett; Stacie A Dalrymple; Simon Lee; Martin Huber Journal: J Biol Chem Date: 2002-04-11 Impact factor: 5.157
Authors: Arianna Nenci; Christoph Becker; Andy Wullaert; Ralph Gareus; Geert van Loo; Silvio Danese; Marion Huth; Alexei Nikolaev; Clemens Neufert; Blair Madison; Deborah Gumucio; Markus F Neurath; Manolis Pasparakis Journal: Nature Date: 2007-03-14 Impact factor: 49.962
Authors: R Beyaert; A Cuenda; W Vanden Berghe; S Plaisance; J C Lee; G Haegeman; P Cohen; W Fiers Journal: EMBO J Date: 1996-04-15 Impact factor: 11.598
Authors: Prodyot K Chatterjee; Michael M Yeboah; Oonagh Dowling; Xiangying Xue; Saul R Powell; Yousef Al-Abed; Christine N Metz Journal: PLoS One Date: 2012-05-07 Impact factor: 3.240