Roles of Toll-Like Receptor 4, IκB Kinase, and the Proteasome in the Intestinal Alterations Caused by Sepsis

Gonzálo, Sergio; Valero, Marta Sofía; Salinas, Fernando Martínez de; Vergara, Claudia Marsella Guzmán; Arruebo, M. P.; Plaza, Miguel Ángel; Murillo, María Divina; Grasa, Laura

doi:10.1007/s10620-014-3418-6

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…The lipopolysaccharide (LPS) from Shigella flexneri and Escherichia coli , both ligands of TLR4, and Pam2CSK4 and Pam3CSK4, which activate TLR2/6 and TLR1/2 heterodimers, respectively, decreased the ACh-induced contractions in primary cultures of colonic human smooth muscle cells [ 34 ]. Additionally, LPS from Escherichia coli can also decrease the contractions induced by ACh in the rabbit duodenum [ 35 , 36 ]. These data suggest that the lack of TLR2 or TLR4 as well as over-activation of these TLRs would reduce the intestinal motility mediated by ACh.…”

Section: Discussionmentioning

confidence: 99%

TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors

Layunta

Forcén

Grasa

2022

Cells

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Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by intestinal dysmotility. Changes in intestinal microbiota (dysbiosis) can lead to alterations in neuro-muscular functions in the gut. Toll-like receptors (TLRs) 2 and 4 recognize intestinal bacteria and are involved in the motor response induced by gastrointestinal (GI) neurotransmitters. Acetylcholine (ACh) is a well-known neurotransmitter involved in the regulation of GI motility. This study aimed to evaluate the role of TLR2 and TLR4 in the intestinal motor-response induced by ACh in the mouse ileum, as well as the expression and function of the muscarinic and nicotinic ACh receptors. Muscle contractility studies showed that the contractions induced by ACh were significantly lower in TLR2−/− and TLR4−/− with respect to WT mice. In WT mice, the contractions induced by ACh were reduced in the presence of AF-DX AF-DX 116 (a muscarinic ACh receptor (mAChR) M2 antagonist), 4-DAMP (a mAChR M3 antagonist), mecamylamine (a nicotinic AChR receptor (nAChR) α3β4 antagonist) and α-bungarotoxin (a nAChR α7 antagonist). In TLR2−/− mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4−/− mice, the contractions induced by ACh were reduced by α-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and α3 receptors were diminished in the ileum from TLR2−/− and TLR4−/− with respect to WT mice. However, the levels of mRNA and protein of β4 were diminished only in TLR4−/− but not in TLR2−/− mice. In conclusion, our results show that TLR2 and TLR4 modulates the motor responses to ACh in the mouse ileum. TLR2 acts on muscarinic M2 and M3 and nicotinic α3β4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic α3β4 and α7 ACh receptors.

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Section: Discussionmentioning

confidence: 99%

TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors

Layunta

Forcén

Grasa

2022

Cells

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“…Intravenous administration of the LPS from E. coli has been widely used as a model of sepsis in several animal species, including monkeys (Imaeda et al, 2002), pigs (Tadros et al, 2000), mice (Arribas et al, 2009;Lyu et al, 2015), rats (Wafa et al, 2015;Li et al, 2016) and rabbits (Gonzalo et al, 2010(Gonzalo et al, , 2015. LPS has been reported to evoke an inflammatory response (Lyu et al, 2015) and decrease the blood flow to the intestine, resulting in ischemic damage in the intestinal mucosa and increased epithelial barrier permeability (Tadros et al, 2000;Wafa et al, 2015;Li et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have revealed that the LPS from E. coli O111:B4 inhibits the motility and contractility of rabbit small intestine by activating the TLR4 (Gonzalo et al, 2015); the p38, ERK, and JNK Mitogen-Activated Protein Kinases (MAPK) pathways (Gonzalo et al, 2010(Gonzalo et al, , 2011a(Gonzalo et al, , 2011b; the IkappaB kinase complex and proteasome W o r l d R a b b i t S c i e n c e (Gonzalo et al, 2015); and, finally, inducing the translocation of nuclear factor kappaB to the nucleus (Hernandez et al, 2011) and evoking the release of interleukins (Hernandez et al, 2011;Gonzalo et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

The lipopolysaccharide from Escherichia coli O127:B8 induces inflammation and motility disturbances in rabbit ileum

et al. 2017

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The aim of this work was to evaluate the effects of lipopolysaccharide (LPS) from Escherichia coli O127:B8 on the expression of toll-like receptor 4 (TLR4), the histology, and motor function in rabbit ileum. Rabbits were injected intravenously with saline or LPS (100 μg/kg, 2 h). The mRNA expression and localization of TLR4 were determined by reverse transcriptase-PCR and immunofluorescence, respectively. Histological damage induced by LPS was evaluated in sections of ileum stained with haematoxylin and eosin. Contractility studies of ileum were performed in an organ bath. The mRNA expression of TLR4 decreased in the muscular but not in the mucosal layer of rabbits treated with LPS. TLR4 was localised in both the mucosal and muscular layers of rabbit ileum. LPS induced intestinal inflammation and altered the spontaneous contractions and the serotonin-, acetylcholine- and KCl-induced contractions. In conclusion, LPS from E. coli O127:B8 induced a decrease in the mRNA expression of TLR4, an inflammatory response, and changes in the contractility of rabbit ileum.

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Unfolding the Mechanism of Proteases in Pathophysiology of Gastrointestinal Diseases

Banerjee

Ghosh

Sinha

et al. 2017

Pathophysiological Aspects of Proteases

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Roles of Toll-Like Receptor 4, IκB Kinase, and the Proteasome in the Intestinal Alterations Caused by Sepsis

Abstract: Toll-like receptor 4, the IκB kinase complex, and the proteasome could be therapeutic targets in the treatment of sepsis symptoms in the intestine.

Cited by 4 publications

References 41 publications

TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors

TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors

The lipopolysaccharide from Escherichia coli O127:B8 induces inflammation and motility disturbances in rabbit ileum

Unfolding the Mechanism of Proteases in Pathophysiology of Gastrointestinal Diseases

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