Cysteinyl leukotriene-receptor-1 antagonists interfere with PGE2 synthesis by inhibiting mPGES-1 activity

Kahnt, Astrid S.; Rörsch, Florian; Diehl, Olaf; Lehmann, Christian; Steinbrink, Svenja D.; Angioni, Carlo; Geißlinger, Gerd; Grösch, Sabine; Steinhilber, Dieter; Maier, Thorsten J.

doi:10.1016/j.bcp.2013.05.005

Cited by 26 publications

(24 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PPARg ratio was also increased under proinflammatory conditions, while levels remained similar in the montelukast-treated and control group. Despite the fact that LPS did significantly increase COX-2 expression, the present data clearly demonstrates a decreased detection of this isoform in the montelukast-treated group under proinflammatory conditions, a result consistent with the known modulatory effect of montelukast on this specific enzyme in other human cells [21]. The 5-LOX was increased under an inflammatory condition which is consistent with the increased leukotrienes production under LPS stimulation observed by Wierzbicki and Brzezinska-Blaszczyk [30].…”

Section: Effect Of Antenatal Montelukast Treatment On Inflammation Masupporting

confidence: 91%

“…In addition to being a cysLTR1 antagonist, montelukast also presents secondary antiinflammatory effects. Indeed, montelukast has been reported to inhibit 5-LOX in inflammatory cells [19,20] and interfere with COX-2 activity, resulting in decreased prostaglandin levels [21]. In 2010, we demonstrated that inhibition of 5-LOX and COX largely reduced contractions in vitro [22].…”

Section: Introductionmentioning

confidence: 64%

See 1 more Smart Citation

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

Corriveau

Blouin

Burt

et al. 2016

European Journal of Obstetrics & Gynecology and Reproductiv

View full text Add to dashboard Cite

show abstract

Section: Effect Of Antenatal Montelukast Treatment On Inflammation Masupporting

confidence: 91%

Section: Introductionmentioning

confidence: 64%

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

Corriveau

Blouin

Burt

et al. 2016

European Journal of Obstetrics & Gynecology and Reproductiv

View full text Add to dashboard Cite

show abstract

“…These results suggest that cPGE 2 may provide PGE 2 essential for cellular homeostasis, while mPGES-1 KO mice had significantly decreased basal PGE 2 production in most organs. A recent study reported that mPGES-1 activity is inhibited in transformed cell lines by cysteinyl leukotriene receptor-1 antagonists; 78 however, this has not been confirmed either in primary cells or in vivo . Studies in KO mice do not support that either cPGES or mPGES-2 are important PGESs enzymes in vivo .…”

Section: Individual Prostanoidsmentioning

confidence: 94%

The role of prostaglandins in allergic lung inflammation and asthma

Claar

Hartert

Peebles³

2014

Expert Review of Respiratory Medicine

104

View full text Add to dashboard Cite

Prostaglandins are products of the cyclooxygenase pathway of arachidonic acid metabolism. There are five primary prostaglandins, PGD2, PGE2, PGF2, PGI2, and thromboxane B2, all of which signal through distinct seven transmembrane, G-protein coupled receptors. Some prostaglandins may counteract the actions of others, or even the same prostaglandin may have opposing physiologic or immunologic effects, depending on the specific receptor through which it signals. In this review, we will examine the effects of cyclooxygenase activity and the various prostaglandins on allergic airway inflammation and physiology that is associated with asthma. We also highlight the potential therapeutic benefit of targeting prostaglandins in allergic lung inflammation and asthma based on basic science, animal model, and human studies.

show abstract

“…These are (i) inhibition of 5-LO, resulting in attenuation of production not only of cysLTs but also of LTB 4 [26, 30, 31]; (ii) nonspecific inhibition of cyclic nucleotide phosphodiesterases (PDEs) [26, 32], resulting in increased levels of 3′,5′-cyclic adenosine monophosphate (cAMP), a major regulator of the proinflammatory activities of cells of the innate immune system [33]; (iii) inhibition of the activity of the transcription factor, NF κ B [29, 34–36]; (iv) inhibition of prostaglandin E synthase [37]; (v) inhibition of eosinophil adhesion and migration [38, 39]; and (vi) antagonism of purinergic P2Y receptors [31]. …”

Section: Cysltr1-independent Anti-inflammatory Mechanisms Of Cysltmentioning

confidence: 99%

“…Montelukast, pranlukast, and zafirlukast, at IC50 concentrations between 2 and 4 μ M, have been reported to inhibit the synthesis of prostaglandin (PG) E 2 by isolated, lipopolysaccharide-activated human leukocytes, as well as by various cytokine-exposed cancer cell lines in vitro , apparently by direct inhibition of microsomal PGE synthase-1 [37]. Aside from cysLTR1-independent anti-inflammatory effects, these observations may also be of significance in relation to the antitumor activities of cysLTR1 antagonists [42].…”

Section: Cysltr1-independent Anti-inflammatory Mechanisms Of Cysltmentioning

confidence: 99%

Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function

Theron

Steel

Tintinger

et al. 2014

Journal of Immunology Research

View full text Add to dashboard Cite

Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8+ cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5′-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.

show abstract

Cysteinyl leukotriene-receptor-1 antagonists interfere with PGE2 synthesis by inhibiting mPGES-1 activity

Cited by 26 publications

References 42 publications

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

The role of prostaglandins in allergic lung inflammation and asthma

Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function

Contact Info

Product

Resources

About