Cyclooxygenase-2 and Inflammation Mediators Have a Crucial Role in Reflux-Related Esophageal Histological Changes and Barrett’s Esophagus

Taddei, Antonio; Fabbroni, Valentina; Pini, Alessandro; Lucarini, Laura; Ringressi, Maria Novella; Fantappiè, Ornella; Bani, Danièle; Messerini, Luca; Masini, Emanuela; Bechi, Paolo

doi:10.1007/s10620-013-2975-4

Cited by 28 publications

(38 citation statements)

References 32 publications

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“…Hence, the restoration of esophageal mucosa integrity represents an efficient and innocuous approach by which GERD could be alleviated. Accumulating studies exploring potential therapeutic targets have highlighted berberine and esophageal mucosal damage in reflux esophagitis caused by suppressing proinflammatory cytokines and cyclooxygenase-2, as well as reflux-related esophageal histological changes and the therapeutic use of melatonin in GERD [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease

Yu¹,

Wang²,

Zhang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Numerous studies have highlighted the activation of NF-κB in the esophageal mucosa during the early stages of gastroesophageal reflux disease (GERD). The present study aimed to investigate the role of the TLR4/NF-κB signaling pathway in GERD rat models. Methods: Wistar rats (n = 60) were recruited to establish a GERD animal model. Distal esophageal pH was assessed, followed by determination of the contents of thiobarbituric acid-reactive species (TBARS) and reactive oxygen species (ROS) in esophageal mucosa homogenate. ELISA was employed to detect the levels of inflammatory factors (IL-6, IL-8, IL-10 and TNF-α) in esophageal mucosa. The expression of MMP-3, MPP-9, Cldn1 and Cldn4 was determined by immunohistochemistry. RT-qPCR and western blot analysis were applied to evaluate the protein expressions in TLR4/NF-κB signaling pathway, while TUNEL staining was utilized to examine the apoptosis rate in the esophageal mucosal tissues. Results: Distal esophageal pH of the rats was higher in the GERD + PDTC group than in other groups. Levels of inflammatory factors in esophageal mucosal tissues were downregulated with the inhibition of NF-κB, which was determined to be associated with the decreased contents of TBARS and ROS. Moreover, decreased MMP-3 and MPP-9 in addition to elevated Cldn1 and Cldn4 were detected in the esophageal mucosa as a result of the inactivation of NF-κB. The TLR4/NF-κB signaling pathway-related proteins (TLR4, NF-κB and IκBα); the rate of apoptosis was demonstrated to be suppressed in the GERD + PDTC group, while inactivating NF-κB was found to alleviate the tissue damage observed in the esophageal mucosa. Conclusion: The key findings of the current study demonstrate that the inactivation of the TLR4/NF-κB signaling pathway alleviates oxidative stress injury and promotes the repair of esophageal mucosal injury among rats with GERD, highlighting a potential novel GERD mechanism.

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Section: Introductionmentioning

confidence: 99%

Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease

Yu¹,

Wang²,

Zhang³

et al. 2018

Cell Physiol Biochem

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“…EAC, therefore, like colon cancer, identifies a multistep cancer model that is being thoroughly studied. The evolution of the sequence has been shown to largely depend upon inflammation and its mediators, such as cyclooxygenase‐2 (COX‐2) . However, although mucosal inflammation can be directly caused by GER, it could also be caused by esophageal microbiome variations induced by GER (see below).…”

Section: Major Esophageal Diseasesmentioning

confidence: 99%

The esophageal microbiota in health and disease

Pilato

Freschi

Ringressi

et al. 2016

Annals of the New York Academy of Sciences

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127

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The esophageal mucosa is among the sites colonized by human microbiota, the complex microbial ecosystem that colonizes various body surfaces and is increasingly recognized to play roles in several physiological and pathological processes. Our understanding of the composition of the esophageal microbiota in health and disease is challenged by the need for invasive sampling procedures and by the dynamic nature of the esophageal environment and remains limited in comparison with the information available for other body sites. Members of the genus Streptococcus appear to be the major components of the microbiota of the healthy esophagus, although the presence of several other taxa has also been reported. Dysbiosis, consisting of enrichment in some Gram-negative taxa (including Veillonella, Prevotella, Haemophilus, Neisseria, Campylobacter, and Fusobacterium), has been reported in association with gastroesophageal reflux disease and is hypothesized to contribute to the evolution of this condition toward Barrett's esophagus (which is the most common esophageal precancerous lesion) and, eventually, adenocarcinoma. Some Campylobacter species (mostly C. concisus) are also putatively involved in the progression of disease toward adenocarcinoma. However, variable findings have recently been reported in additional studies. Causative relationships between dysbiosis or specific bacterial species and esophageal diseases remain controversial and warrant further investigations.

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“…However the mechanisms that underlie this progression need to be defined. Despite many molecules have been widely studied such as COX-2 [11], Herg1 [12], bcl-2 and bcl-xL [13], no conclusive studies are present literature. This is partly due to inter individual variability in humans and to the difficulties both in surveillance and in the interpretation of the endoscopic and histologic findings.…”

Section: Discussionmentioning

confidence: 99%

A Mouse Model for Barrett’s Esophagus: Surgery and Histology

Taddei¹,

Lottini²,

Fazi³

et al. 2017

J Carcinog Mutagen

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Purpose: Barrett's esophagus (BE) is the sole precursor lesion of esophageal adenocarcinoma (EA) identified so far. The progression towards EA is estimated to affect 2 to 10% of BE patients, hence endoscopic surveillance of at-risk subjects is mandatory. Surveillance endoscopic procedures imply high cost, discomfort and risks for the patient, as well as the non-infrequent missing of small, focal lesions signaling progression to EA. Hence, it is important to search for new potential markers to better identify BE patients at risk of EA progression. The aim of this study was to produce a mouse model of BE, suitable for further molecular and genetic analyses.Methods: Forty-four CD1 mice were operated upon by means of an esophago-jejunal anastomosis. Five CD1 mice underwent a sham operation. The animals were sacrificed 10 months later and histological analysis was performed with Hematoxylin & Eosin and Alcian Blue staining. Results:The overall postoperative mortality rate was 11%. Of the 39 operated animals 14% developed histologically detectable intestinal metaplasia in the lower esophagus. No histologically detectable lesions were shown in the sham group.Conclusions: The mice model we propose could be applied because of its technical feasibility and acceptable mortality and can be used in transgenic mice too, in order to better understand molecular progression from BE to esophageal adenocarcinoma.

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Cyclooxygenase-2 and Inflammation Mediators Have a Crucial Role in Reflux-Related Esophageal Histological Changes and Barrett’s Esophagus

Cited by 28 publications

References 32 publications

Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease

Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease

The esophageal microbiota in health and disease

A Mouse Model for Barrett’s Esophagus: Surgery and Histology

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