Endogenous Endotoxin Participates in Causing a Panenteric Inflammatory Ileus After Colonic Surgery

Türler, Andreas; Schnurr, Christoph; Nakao, Atsunori; Tögel, Sandra; Moore, Beverley A.; Murase, Noriko; Kalff, Jörg C.; Bauer, Anthony J.

doi:10.1097/01.sla.0000255595.98041.6b

Cited by 51 publications

(46 citation statements)

References 36 publications

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“…The motility alterations at distance of an inflammatory region we reported here bear resemblance to the panenteric field effect as described for postoperative and septic ileus and may possibly involve similar pathophysiological mechanisms (10,15,52).…”

Section: Discussionmentioning

confidence: 65%

TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats

Schepper¹,

Man²,

Ruyssers³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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BY. TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats. Am J Physiol Gastrointest Liver Physiol 294: G245-G253, 2008. First published November 8, 2007 doi:10.1152/ajpgi.00351.2007.-Rats with experimental colitis suffer from impaired gastric emptying (GE). We previously showed that this phenomenon involves afferent neurons within the pelvic nerve. In this study, we aimed to identify the mediators involved in this afferent hyperactivation. Colitis was induced by trinitrobenzene sulfate (TNBS) instillation. We determined GE, distal front, and geometric center (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. We evaluated the effects of the transient receptor potential vanilloid type 1 (TRPV1) antagonists capsazepine (5-10 mg/kg) and N- (4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 1-10 mg/kg) and the calcitonin generelated peptide (CGRP) receptor antagonist CGRP-(8-37) (150 g/ kg). To determine TRPV1 receptor antagonist sensitivity, we examined their effect on capsaicin-induced relaxations of isolated gastric fundus muscle strips. Immunocytochemical staining of TRPV1 and RT-PCR analysis of TRPV1 mRNA were performed in dorsal root ganglion (DRG) L6 -S1. TNBS-induced colitis reduced GE but had no effect on intestinal motility. Capsazepine reduced GE in controls but had no effect in rats with colitis. At doses that had no effects in controls, BCTC and CGRP-(8-37) significantly improved colitis-induced gastroparesis. Capsazepine inhibited capsaicininduced relaxations by 35% whereas BCTC completely abolished them. TNBS-induced colitis increased TRPV1-like immunoreactivity and TRPV1 mRNA content in pelvic afferent neuronal cell bodies in DRG L6 -S1. In conclusion, distal colitis in rats impairs GE via sensitized pelvic afferent neurons. We provided pharmacological, immunocytochemical, and molecular biological evidence that this sensitization is mediated by TRPV1 receptors and involves CGRP release. gastric emptying; sensory nerve; pelvic nerve; CGRP PATIENTS WITH INFLAMMATORY bowel disease (IBD) often suffer from disorders of gastrointestinal motility and sensitivity, imposing a significant load on the patient's quality of life (20). These alterations are known to appear both during inflammatory episodes and in periods of remission and can occur either at the site of inflammation or at a distance from this site (43). Especially concerning the latter situation, little is known about the underlying pathophysiological mechanisms. There have been several studies documenting the effects of isolated experimental colitis on small intestinal neuromuscular function, but the in vivo consequences on gut transit were inconclusive (3, 5, 29). McHugh et al. (37) reported that rats with trinitrobenzene sulfate (TNBS)-induced colitis suffer from a reduction of gastric emptying but did not investigate the underlying mechanisms. We recently confirmed that rats with experimental...

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Section: Discussionmentioning

confidence: 65%

TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats

Schepper¹,

Man²,

Ruyssers³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Another hint to the involvement of luminal pathogens was also shown by Türler et al in a model of colonic manipulation [60]. One should note that this model differs from the more commonly used small bowel manipulation as the large bowel contains log numbers more bacteria and bacterial degradation product that can act as innate immune stimuli.…”

Section: Barrier Dysfunctionmentioning

confidence: 88%

Immune mediators of postoperative ileus

Wehner

Vilz

Stoffels

et al. 2012

Langenbecks Arch Surg

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“…Surgical manipulation of the colon initiates a complex inflammatory cascade within the colonic muscularis, which is characterized by the release of inflammatory mediators and the recruitment of leukocytes (Tü rler et al, 2002). Recently, it was shown that selective colonic manipulation also initiates a distant inflammatory response in the small intestinal muscularis that significantly contributes to the pan-enteric development of POI (Tü rler et al, 2007). Therefore, we sought to determine whether the postoperative inflammatory response within both the colonic and small intestinal muscularis, which has been shown to settle within 6 to 24 h after surgical manipulation, would be altered by rosiglitazone treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Despite this novel insight, there is no pharmacological treatment yet available to prevent this postoperative event. In the present study, we Previous studies have demonstrated that surgical manipulation of the colon initiates an inflammatory cascade within both the colonic and small intestinal muscle layer that consists of 1) the induction of proinflammatory cytokines, chemokines, and adhesion molecules; 2) the additional recruitment of circulating leukocytes into the muscularis; and 3) the release of kinetically active substances, such as NO and prostaglandins, that directly inhibit smooth muscle contractility (Tü rler et al, 2002(Tü rler et al, , 2007Bauer and Boeckxstaens, 2004). Herein, we show that pretreatment of mice with rosiglitazone significantly attenuates these intestinal muscularis inflammatory responses, an effect that was abrogated by the PPAR␥ antagonist GW9662.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor γ Activation Alleviates Postoperative Ileus in Mice by Inhibition of Egr-1 Expression and Its Downstream Target Genes

Elinck¹,

Priem²,

Leybaert³

et al. 2009

J Pharmacol Exp Ther

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Postoperative ileus, a major cause of morbidity after abdominal surgery, is characterized by intestinal dysmotility and a complex inflammatory cascade within the intestinal muscularis. Treatment with carbon monoxide (CO)-inhaled or intraperitoneal-has been shown to ameliorate bowel dysmotility caused by surgical manipulation of the gut in experimental animals. Recent evidence indicates that CO exerts its anti-inflammatory effects through the induction of peroxisome proliferator-activated receptor (PPAR)-␥, a nuclear receptor whose activation has been linked to several physiological pathways, including those related to the regulation of intestinal inflammation. The purpose of this study was to evaluate pharmacological activation of PPAR␥ in a murine model of postoperative ileus by use of the PPAR␥ agonist rosiglitazone. Postoperative bowel dysmotility was induced by surgical manipulation of the colon. The functional severity of postoperative ileus was significantly ameliorated in mice pretreated with rosiglitazone (0.3 to 10 mg/kg i.p.); this was associated with a down-regulation of pro-inflammatory cytokines/chemokines, inducible nitric oxide synthase activity, cyclooxygenase-2 activity, as well as a decrease in leukocyte recruitment into the muscularis of both colon and jejunum. These anti-inflammatory effects were preceded by a PPAR␥-dependent down-regulation of early growth response (Egr)-1, a key regulator of inflammatory gene expression. In conclusion, these results indicate that rosiglitazone significantly attenuates postoperative ileus in mice by suppression of the muscularis inflammatory cascade through a PPAR␥-dependent down-regulation of Egr-1 and encourage the further clinical evaluation of synthetic PPAR␥ agonists as pharmacological tool to prevent this postoperative event.

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Endogenous Endotoxin Participates in Causing a Panenteric Inflammatory Ileus After Colonic Surgery

Cited by 51 publications

References 36 publications

TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats

TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats

Immune mediators of postoperative ileus

Peroxisome Proliferator-Activated Receptor γ Activation Alleviates Postoperative Ileus in Mice by Inhibition of Egr-1 Expression and Its Downstream Target Genes

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