Inflammatory Mediators in Gastrointestinal Defense and Injury

Wallace, John L.; Ma, Li

doi:10.1177/153537020122601107

Cited by 108 publications

(83 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…14 The central importance of prostaglandins in epithelial mucosal function has been demonstrated by the ulcerogenic effect of nonsteroidal antiinflammatory drugs (NSAIDS) in the gastrointestinal tract. [15][16][17] This is consistent with the protective effect of prostaglandins against ulcers in the gastrointestinal tract of both human and animal models. 18 -21 Elevated concentrations of prostaglandins in IBD were first described by Gould et al, 22 and confirmed by others.…”

Section: Discussionsupporting

confidence: 69%

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

Hatoum

Gauthier

Binion

et al. 2005

ATVB

View full text Add to dashboard Cite

Objective-Endothelium-dependent dilation to acetylcholine (Ach) is reduced in mucosal arterioles from patients with inflammatory bowel disease (IBD). The contributions of both nitric oxide (NO) and endothelial-derived hyperpolarizing factor (EDHF) are decreased. We hypothesized that the remaining dilation results from products of cyclooxygenase. Methods and Results-High-performance liquid chromatography (HPLC) was used to isolate eicosanoid vasodilator products and videomicroscopy was used to examine vasomotor responses in human mucosal arterioles from subjects with or without IBD undergoing bowel resection surgeries. In subjects without IBD, Ach constricted (Ϫ52%Ϯ10%) arterioles devoid of endothelium. Indomethacin (INDO) (cyclooxygenase inhibitor) had no effect. In contrast, Ach dose-dependently dilated both intact and endothelial denuded arterioles from patients with IBD. The dilation was converted to constriction by INDO (Ϫ54%Ϯ9%; PϽ0.05 versus non-IBD) or by BWA868C (PGD 2 receptor antagonist). Only in arterioles from subjects with IBD did Ach produce an arachidonic acid metabolite that comigrated on HPLC with PG D 2 (PGD 2 ). Exogenous PGD 2 dilated (maxϭ66%Ϯ4%) IBD arterioles. Conclusion-In arterioles from IBD patients, Ach-mediated dilation shifts from endothelial production of NO and EDHF to nonendothelial generation of a PG, likely PGD 2 . This is a novel dilator mechanism arising from nonendothelial vascular tissue that compensates for loss of endothelium-dependent dilation. PGD 2 appears to be important in regulating mucosal blood flow in patients with IBD, implicating potentially detrimental effects from nonsteroidal antiinflammatory drugs. Key Words: cyclooxygenase Ⅲ inflammatory bowel disease Ⅲ microcirculation Ⅲ prostaglandin Ⅲ vasodilation E ndothelium-dependent vasorelaxation plays a critical role in regulating tissue perfusion. 1 Impaired vasorelaxation is a key feature of microvascular dysfunction that contributes to the pathophysiology of diabetes mellitus, hyperlipidemia, and atherosclerosis. 2,3 A new association of microvascular dysfunction with clinical inflammatory bowel disease (IBD) (Crohn disease, ulcerative colitis) has been made. 4 IBD is characterized by refractory, poorly healing mucosal ulcerations, and impaired endothelium-mediated vasorelaxation. 4,5 Using in vitro dimension measurements of cannulated 50 to 200 m arterioles, we have demonstrated that normal intestinal microvessels dilate in response to the classic endothelium-dependent agonist, acetylcholine (Ach). 4 After inhibiting nitric oxide (NO) synthase, cyclooxygenase (COX), and hyperpolarization mechanisms, or after endothelial denudation, constriction was observed. Microvessels isolated from chronically inflamed IBD tissue demonstrated loss of NO-mediated and hyperpolarization-mediated vasodilation in response to Ach. However, in contrast to vessels from subjects without IBD or from uninvolved segments of bowel from patients with IBD, arterioles from active IBD segments had attenuated dilation to Ach that was independ...

show abstract

Section: Discussionsupporting

confidence: 69%

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

Hatoum

Gauthier

Binion

et al. 2005

ATVB

View full text Add to dashboard Cite

show abstract

“…Conceivably, the increase in oxidative stress in the aforementioned groups was shown, in the current study, by SOD concentration. It has also been demonstrated that LTB4 intracolonic administration provokes increased tissue damage in rats with colitis and that LTB4 antagonist utilization as well as 5-LPO inhibitors can attenuate leukocytes adhesion and reduce colonic damage severity induced by NSAIDs (54) . In the present experiment, there were no significant differences in LTB4 concentration when the control group was compared to the colitis group, similarly to the results obtained by Nieto et al (41) in experimental colitis induced by TNBS.…”

Section: Discussionmentioning

confidence: 99%

COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

Breganó

Barbosa

Kadri

et al. 2014

Arq. Gastroenterol.

View full text Add to dashboard Cite

-Context -Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objective -The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods -Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results -The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions -Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be involved in the exacerbation of experimental colitis by nonselective nonsteroidal anti-inflammatory drugs. HEADINGS -Colitis. Non-steroidal anti-inflammatory agents. Eicosanoids. Oxidative stress.

show abstract

“…In addition, it is reported that those cytokines are produced from inflammatory sites, functioning as inflammatory mediators in the process of gastric ulcer healing. 13,26,27,28 Taken together, it is reasonable to speculate that these inflammatory cytokines were secreted from the site of the injury and delivered to the cells located around the ulcerated craters, resulting in the activation of the Tg promoter (hCMV promoter). We confirmed that these cytokine genes are indeed upregulated in Tg stomachs in response to HCl/ethanol administration ( Figure 5c).…”

Section: Discussionmentioning

confidence: 99%

In vivo evidence for the role of RegI in gastric regeneration: transgenic overexpression of RegI accelerates the healing of experimental gastric ulcers

Fukuhara

Kadowaki

Ose

et al. 2010

Laboratory Investigation

View full text Add to dashboard Cite

On the basis of its temporal and spatial pattern of expression during the healing of gastric ulcers, RegI is implied to be a key growth factor governing the gastric progenitor cell proliferation, which is fundamental for reconstruction of the gastric tissue; however, there is no direct in vivo evidence. The aim of this study was to use RegI-transgenic (Tg) mice to test the role of RegI protein in the healing of experimentally induced gastric ulcers. The stomachs from 48 pairs of wildtype (Wt) and Tg littermates were examined for gastric erosions after 24 h of water-immersion stress, or, 6, 12, 18 and 24 h after oral administration of HCl/ethanol. Expression levels of c-fos and c-myc proto-oncogenes were examined over time by real-time reverse transcriptase PCR to assess gastric cell proliferation. Almost all the littermate pairs tested showed superiority of Tg mice over Wt mice in the ability of decreasing ulcer index (UI) (cumulative length of erosion). The timecourse study revealed that the UIs of Tg were lower in the healing phase, and not in the injury phase. The fraction of proliferating cells was higher in Tg mice than in Wt mice throughout the time course as assessed by c-fos expression levels. This is the first in vivo evidence that RegI has a role in gastric ulcer healing. We suggest that RegI exerts its effects by promoting growth and not by cytoprotection.

show abstract

Inflammatory Mediators in Gastrointestinal Defense and Injury

Cited by 108 publications

References 160 publications

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

In vivo evidence for the role of RegI in gastric regeneration: transgenic overexpression of RegI accelerates the healing of experimental gastric ulcers

Contact Info

Product

Resources

About