Anti-inflammatory and analgesic activity of a novel inhibitor of microsomal prostaglandin E synthase-1 expression

Guerrero, María Dolores Chamorro; Aquino, Maurizio; Bruno, Ines; Riccio, Raffaele; Terencio, María Carmen; Payá, Miguel

doi:10.1016/j.ejphar.2009.08.007

Cited by 35 publications

(26 citation statements)

References 35 publications

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“…We demonstrate here mPGES-1 mRNA expression in Calu-3 cells, as well as suggest a possible role in mediating the H 2 O 2 -stimulated efflux response. In the present study we used two compounds previously reported as selective inhibitors of mPGES-1: Cay10526 and Cay10589 (Guerrero et al, 2009). These compounds have different mechanisms of action, Cay10589 by direct inhibition of the enzyme and Cay10526, which decreases gene expression and thus inhibits production.…”

Section: Discussionmentioning

confidence: 99%

“…3A). We next investigated the potential role for this enzyme by using 2- [[4-[([1,1Ј-biphenyl]-4-ylmethyl)amino]-6-chloro-2-pyrimidinyl]thio]-octanoic acid (Cay10589), a reported mPGES-1 inhibitor, and Cay10526, which decreases mPGES-1 expression (Guerrero et al, 2009). In the presence of Cay10589 (5 M), the H 2 O 2 -stimulated response was significantly inhibited (Fig.…”

Section: H 2 O 2 -Stimulated Efflux Is Abolished By Cox-1 Butmentioning

confidence: 99%

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The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

Jones

Li²,

Cowley³

2012

J Pharmacol Exp Ther

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Oxidative stress is implicated in the pathogenesis of many inflammatory pulmonary diseases, including cystic fibrosis (CF). Delineating how oxidative stress stimulates CF transmembrane conductance regulator (CFTR) in airway epithelial cells is useful, both to increase the understanding of airways host defense and suggest therapeutic approaches to reduce the oxidant stress burden in the CF lung. Using the airway epithelial cell line Calu-3, we investigated the hypothesis that hydrogen peroxide (H 2 O 2 ), which stimulates anion efflux through CFTR, does so via the production of prostaglandin E 2 (PGE 2 ). Using iodide efflux as a biochemical marker of CFTR activity and short circuit current (I sc ) recordings, we found that the H 2 O 2 -stimulated efflux was abolished by cyclooxygenase-1 inhibition and potentially also involves microsomal prostaglandin E synthase-1 activity, implicating a role for PGE 2 production. Furthermore, H 2 O 2 application resulted in a rapid release of PGE 2 from Calu-3 cells. We additionally hypothesized that the PGE 2 subtype 4 (EP 4 ) receptor was involved in mediating this response. In the presence of (4Z)-7-[(rel-1S,2S,5R)-5-((1,1Ј-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848) (which blocks the EP 4 receptor), the H 2 O 2 -stimulated response was abolished. To investigate this finding in a polarized system, we measured the increase in I sc induced by H 2 O 2 addition in the presence and absence of AH23848. H 2 O 2 induced a robust increase in I sc , which was significantly attenuated in the presence of AH23848, suggesting some role for the EP 4 receptor. In conclusion, with H 2 O 2 as a model oxidant stress, stimulation of CFTR seems to involve PGE 2 production and likely EP 4 receptor activation in Calu-3 airway epithelial cells. This mechanism would be compromised in the CF airways.

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Section: Discussionmentioning

confidence: 99%

Section: H 2 O 2 -Stimulated Efflux Is Abolished By Cox-1 Butmentioning

confidence: 99%

The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

Jones

Li²,

Cowley³

2012

J Pharmacol Exp Ther

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“…193) (from green tea) have been shown to affect mPGES-1 in vitro. Several mPGES-1 inhibitors are being studied in animal models, but none are as yet available for use in humans ( Refs 194,195,196,197). In experimental periodontitis in rats, the mPGES-1 inhibitor curcumin effectively inhibited cytokine gene expression at the mRNA and the protein level and inhibited activation of NF-κB in the gingival tissues although the inhibitor did not prevent alveolar bone resorption (Ref.…”

Section: Inhibition Of Inflammatory Mediator Pgementioning

confidence: 99%

Inflammatory mediators in the pathogenesis of periodontitis

Yucel‐Lindberg

Båge

2013

Expert Rev. Mol. Med.

352

334

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Periodontitis is a chronic inflammatory condition of the periodontium involving interactions between bacterial products, numerous cell populations and inflammatory mediators. It is generally accepted that periodontitis is initiated by complex and diverse microbial biofilms which form on the teeth, i.e. dental plaque. Substances released from this biofilm such as lipopolysaccharides, antigens and other virulence factors, gain access to the gingival tissue and initiate an inflammatory and immune response, leading to the activation of host defence cells. As a result of cellular activation, inflammatory mediators, including cytokines, chemokines, arachidonic acid metabolites and proteolytic enzymes collectively contribute to tissue destruction and bone resorption. This review summarises recent studies on the pathogenesis of periodontitis, with the main focus on inflammatory mediators and their role in periodontal disease.

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“…mPGES-1 inhibition is achieved by two methods: 1) PGE 2 production could either be prevented by inhibition of mPGES-1 activity, or 2) by suppression of mPGES-1 transcription and therefore protein expression [4][5][6]. DMC has been shown to inhibit both mPGES-1 activity and its expression [1].…”

Section: Page 4 Of 29mentioning

confidence: 99%

Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-κB

Deckmann

Rörsch

Steri

et al. 2010

Biochemical Pharmacology

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Anti-inflammatory and analgesic activity of a novel inhibitor of microsomal prostaglandin E synthase-1 expression

Cited by 35 publications

References 35 publications

The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

Inflammatory mediators in the pathogenesis of periodontitis

Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-κB

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Anti-inflammatory and analgesic activity of a novel inhibitor of microsomal prostaglandin E synthase-1 expression

Cited by 35 publications

References 35 publications

The Prostaglandin E2Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

The Prostaglandin E2Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

Inflammatory mediators in the pathogenesis of periodontitis

Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-κB

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Product

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The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells