Importance of cyclooxygenase‐1/prostacyclin in modulating gastric mucosal integrity under stress conditions

Amagase, Kikuko; Izumi, Nahoko; Takahira, Yuka; Wada, Tomoko; Takeuchi, Koji

doi:10.1111/jgh.12767

Cited by 13 publications

(12 citation statements)

References 42 publications

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“…In this study, we found that both COX-1 and COX-2 expressions were decreased in SII-Reb and SII-Sal groups at day 5, which indicated that the inhibition of COX (including both COX-1 and COX-2) might underlie the mechanism of aspirin-induced SII ( Fig 4A–4F ). Some investigators suggested that COX-1 to a greater extent than COX-2 contributes to gastric PGE 2 production [ 37 ]. But Castlestone et al demonstrated that, in the intestinal mucosa, the increased production of PGE 2 depended more on COX-2 than on COX-1 [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

Lai

et al. 2015

PLoS ONE

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BackgroundThe effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage.MethodsBALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.ResultsCOX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05).ConclusionRebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

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Section: Discussionmentioning

confidence: 99%

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

Lai

et al. 2015

PLoS ONE

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“…This suggests that the PGE 2 inhibiting effects of KIT 17 and most likely by the other KIT compounds is not due a direct inhibition of COX activity. The COX-1 inducing effects might even have positive benefits, since COX-1 is protecting the gut mucosa and its inhibition by some NSAIDs cause gastro-intestinal side effects [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells

Saliba

Jauch

Gargouri

et al. 2018

J Neuroinflammation

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BackgroundNeuroinflammation plays a vital role in Alzheimer’s disease and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system, and they play essential roles in the maintenance of homeostasis and responses to neuroinflammation. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia. However, its effects on neuroinflammation, mainly on the production of members of the arachidonic acid pathway in activated microglia, have not been elucidated in detail.MethodsIn this present study, a series of coumarin derivatives, that exhibit GPR55 antagonism properties, were designed. The effects of these compounds on members of the arachidonic acid cascade were studied in lipopolysaccharide (LPS)-treated primary rat microglia using Western blot, qPCR, and ELISA.ResultsWe demonstrate here that the various compounds with GPR55 antagonistic activities significantly inhibited the release of PGE2 in primary microglia. The inhibition of LPS-induced PGE2 release by the most potent candidate KIT 17 was partially dependent on reduced protein synthesis of mPGES-1 and COX-2. KIT 17 did not affect any key enzyme involved on the endocannabinoid system. We furthermore show that microglia expressed GPR55 and that a synthetic antagonist of the GPR receptor (ML193) demonstrated the same effect of the KIT 17 on the inhibition of PGE2.ConclusionsOur results suggest that KIT 17 is acting as an inverse agonist on GPR55 independent of the endocannabinoid system. Targeting GPR55 might be a new therapeutic option to treat neurodegenerative diseases with a neuroinflammatory background such as Alzheimer’s disease, Parkinson, and multiple sclerosis (MS).Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1362-7) contains supplementary material, which is available to authorized users.

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“…These results are, to some extent, in agreement with the data obtained by Tanaka et al (2007) [28] who demonstrated that mild stress protects against CRS-induced gastric ulceration by PGs derived from both COX-1 and COX-2 through activation of phospholipase A2. Furthermore, Amagase et al (2014) [29] revealed that PGs derived from COX-1 play an important role in the gastric mucosal defense during CRS. On the contrary, it has been reported that COX-2 plays a crucial role in gastric mucosal defense [30].…”

Section: Discussionmentioning

confidence: 99%

Age-dependent Role of Cilostazol on Cold Restraint Stress-induced Gastric Ulceration in Female Rats

2019

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Introduction: Cilostazol (CIL), a phosphodiesterase III inhibitor, is a potent antiplatelet drug which possesses vasodilator and anti-inflammatory activity that making it an effective drug in gastric ulcer protection. Objectives: This study investigated the influence of age on the effects of CIL against cold restraint stress (CRS)-induced gastric ulcer in rats. Methods: CIL (10 mg/kg/day) was administered orally for 2 weeks to adult and aged female rats before CRS-induced gastric ulcer. Results: This syudy showed that CIL exhibited gastroprotective effects in both adult and aged rats as evidenced by significant decrease in ulcer index, gastric mucosal malondialdehyde level, myeloperoxidase activity and tumor necrosis factor-α protein expression with concomitant increase in gastric mucosal reduced glutathione level and glutathione peroxidase activity, nitric oxide, prostaglandin E2 level, cyclooxygenase-1 and 2 protein expression and gastric juice mucin concentration compared to adult and aged CRS rats, respectively. Additionally, the histopathological examination results came to confirm the protection afforded by CIL in CRS-induced gastric ulcer. Conclusion: The possible protective effect of CIL against CRS-induced gastric ulceration in both adult and aged rat's may be explained via its antioxidant and antiinflammatory properties and by enhancement of gastric mucus secretion. It could be recommended that CIL is considered as a more proper antiplatelet drug for adult and elderly patients who are at risk of gastric ulceration.

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Importance of cyclooxygenase‐1/prostacyclin in modulating gastric mucosal integrity under stress conditions

Cited by 13 publications

References 42 publications

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells

Age-dependent Role of Cilostazol on Cold Restraint Stress-induced Gastric Ulceration in Female Rats

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