Prostanoid production via COX-2 as a causative mechanism of rodent postoperative ileus

Schwarz, Nicolas T.; Kalff, Jörg C.; Türler, Andreas; Engel, B.; Watkins, Simon C.; Billiar, Timothy R.; Bauer, Anthony J.

doi:10.1053/gast.2001.29605

Cited by 233 publications

(259 citation statements)

References 65 publications

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“…Results from our earlier work demonstrated the functional importance of endogenously released nitric oxide and prostaglandins from the inflamed postoperative bowel 11,20 . Therefore, we sought to determine if the generation of these two kinetically active smooth muscle inhibitors would also be altered in the absence of Egr-1.…”

Section: Egr-1 Dependent Inflammatory Mediatorsmentioning

confidence: 90%

“…We have previously seen that nitric oxide and prostanoids from their respective inducible synthases, iNOS and PGHS-2, play a significant mediator role in causing postoperative muscle dysfunction 11,20 . Here we show that the release of nitric oxide and prostanoids from the inflamed muscularis externa after surgical manipulation is significantly dependent on Egr-1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…Our ELISA assay for prostanoids showed a marked induction after surgery, which was significantly diminished in the Egr-1 deficient animals. Our previous experiments using selective iNOS and PGHS-2 inhibitors have demonstrated that the end-products of these synthases can directly inhibit gastrointestinal motility 11 . But, we also hypothesize that these molecules could also play early signaling roles in the inflammatory processes within the manipulated muscularis externa.…”

Section: Discussionmentioning

confidence: 99%

“…Confirmed results demonstrate that simple surgical handling of the intestine activates the dense network of normally resident muscularis macrophages, which subsequently orchestrates a succession of molecular inflammatory responses. These responses include the triggering of the mitogen-activated protein kinase pathways (ERK1/2, p38 and JNK) 7 , the activation of transcription factors (NF-κB, NF-IL6, STAT3) 8 , the recruitment of leukocytes into the manipulated muscularis externa via MCP-1, MIP-1 and ICAM-1 up regulation, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6 8 within the intestinal wall that could alter enteric ganglionic and neuromuscular transmission 9 , and the secretion of the kinetically active inhibitory substances, such as nitric oxide (iNOS) 10 and prostaglandins (COX-2) 11 .…”

Section: Introductionmentioning

confidence: 99%

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Proinflammatory Role of Leukocyte-Derived Egr-1 in the Development of Murine Postoperative Ileus

et al. 2008

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Section: Egr-1 Dependent Inflammatory Mediatorsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proinflammatory Role of Leukocyte-Derived Egr-1 in the Development of Murine Postoperative Ileus

et al. 2008

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“…Most of them focused on singular proinflammatory mediators, such as IL-6 (88), and adhesion molecules and chemokines, such as ICAM-1 (36) and MCP-1 (84). Some authors described inhibitory kinetic factors such as nitric oxide or prostaglandins (39,42,71). Most of these strategies showed subsequent improvement of POI, but their clinical implementation has so far failed to display benefits for the patients (57).…”

Section: Discussionmentioning

confidence: 99%

Impact of CCR7 on the gastrointestinal field effect

Koscielny

Engel

Maurer

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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.2010.-Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7Ϫ/Ϫ and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3ϩCD25ϩ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7 Ϫ/Ϫ mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7 Ϫ/Ϫ animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7 Ϫ/Ϫ mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3ϩCD25ϩ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7Ϫ/Ϫ mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE. postoperative ileus; chemokine receptor 7 POSTOPERATIVE ILEUS (POI) is an inevitable sequela of abdominal surgery or trauma with a variably gradual manifestation. It leads to postoperative discomfort, prolonged hospitalization, and increased patient morbidity and has a high impact on socioeconomic costs (27,43,49,63). The pathophysiology of POI and postoperative gastrointestinal dysmotility, respectively, has been elucidated in recent years. POI is marked by a neurogenic phase and a clinically relevant prolonged inflammatory phase. Both the neuronal activation by intestinal manipulation (IM) and inflammatory cell infiltrates in the intestinal muscularis compromise gastrointestinal motility. These detrimental alterations are emphasized as major factors in the development of POI (4,8,9,15,16,[35][36][37][38][40][41][42]. We reported a time-and trauma-degree-dependent inflammatory cascade (35, 36); infiltration of leukocytes (40 -42...

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Mechanisms and Treatment of Postoperative Ileus

Luckey¹

2003

Arch Surg

388

336

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To review the pathogenesis and treatment of postoperative ileus. Data Sources: Data collected for this review were identified from a MEDLINE database search of the Englishlanguage literature. The exact indexing terms were "postoperative ileus," "treatment," "etiology," and "pathophysiology." Previous review articles and pertinent references from those articles were also used. Study Selection: All relevant studies were included. Only articles that were case presentations or that mentioned postoperative ileus in passing were excluded.

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Prostanoid production via COX-2 as a causative mechanism of rodent postoperative ileus

Cited by 233 publications

References 65 publications

Proinflammatory Role of Leukocyte-Derived Egr-1 in the Development of Murine Postoperative Ileus

Proinflammatory Role of Leukocyte-Derived Egr-1 in the Development of Murine Postoperative Ileus

Impact of CCR7 on the gastrointestinal field effect

Mechanisms and Treatment of Postoperative Ileus

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