Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

Cadieux, Jean-Sébastien; Leclerc, P.; St-Onge, Mireille; Dussault, Andrée-Anne; Laflamme, Christian; Picard, Serge; Ledent, Catherine; Borgeat, Pierre; Pouliot, Marc

doi:10.1242/jcs.01737

Cited by 50 publications

(52 citation statements)

References 60 publications

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“…It has been described that GPER activation promotes adenylate cyclase activation (8). In addition, stimuli known to elevate intracellular cAMP levels, such as PGE 2 , adenosine, and isoproterenol, positively modulate the PTGS2 expression (63)(64)(65). In support of this mechanism, we observed that G1 promoted the phosphorylation of CREB and that the induction of PTGS2 and the phosphorylation of CREB were both mimicked by dbcAMP, a cell-permeant cAMP analog.…”

Section: Discussionsupporting

confidence: 78%

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Estrogen Signaling through the G Protein–Coupled Estrogen Receptor Regulates Granulocyte Activation in Fish

Cabas

Rodenas

Abellán

et al. 2013

The Journal of Immunology

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Neutrophils are major participants in innate host responses. It is well known that estrogens have an immune-modulatory role, and some evidence exists that neutrophil physiology can be altered by these molecules. Traditionally, estrogens act via classical nuclear estrogen receptors, but the identification of a G protein–coupled estrogen receptor (GPER), a membrane estrogen receptor that binds estradiol and other estrogens, has opened up the possibility of exploring additional estrogen-mediated effects. However, information on the importance of GPER for immunity, especially, in neutrophils is scant. In this study, we report that gilthead seabream (Sparus aurata L.) acidophilic granulocytes, which are the functional equivalent of mammalian neutrophils, express GPER at both mRNA and protein levels. By using a GPER selective agonist, G1, it was found that GPER activation in vitro slightly reduced the respiratory burst of acidophilic granulocytes and drastically altered the expression profile of several genes encoding major pro- and anti-inflammatory mediators. In addition, GPER signaling in vivo modulated adaptive immunity. Finally, a cAMP analog mimicked the effects of G1 in the induction of the gene coding for PG-endoperoxide synthase 2 and in the induction of CREB phosphorylation, whereas pharmacological inhibition of protein kinase A superinduced PG-endoperoxide synthase 2. Taken together, our results demonstrate for the first time, to our knowledge, that estrogens are able to modulate vertebrate granulocyte functions through a GPER/cAMP/protein kinase A/CREB signaling pathway and could establish therapeutic targets for several immune disorders in which estrogens play a prominent role.

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Section: Discussionsupporting

confidence: 78%

“…No symbol or "ns" means not significant. consequence of the complex regulatory mechanisms of CREB activation/deactivation (63). Thus, the activation of the protein phosphatase involved in the dephosphorylation of CREB also depends on PKA activity (66,67).…”

Section: Discussionmentioning

confidence: 99%

Estrogen Signaling through the G Protein–Coupled Estrogen Receptor Regulates Granulocyte Activation in Fish

Cabas

Rodenas

Abellán

et al. 2013

The Journal of Immunology

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“…7B) or t=4 h (data not shown). Moreover, activation of the A 2A adenosine receptor, which potentiates COX-2 expression in these conditions [13,30], also failed to significantly alter the expression of mPGES-1 (Fig. 7C).…”

Section: Constitutive Expression Of Mpge Synthase-1 In Neutrophilsmentioning

confidence: 91%

“…Reverse-transcription and real-time PCR were performed essentially as described in [30]. Briefly, first strand cDNA synthesis was performed using 1 μg of total RNA with Superscript II (Invitrogen Lifetechnology, Carlsbad, CA, USA) in recommended conditions, using 500 ng of random hexamers.…”

Section: Real-time Pcrmentioning

confidence: 99%

Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils

St-Onge

Flamand

Biarc

et al. 2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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In the present study, we characterized the generation of prostaglandin (PG)E 2 in human neutrophils. We found that the Ca 2+ -dependent type IV cytosolic phospholipase A 2 (cPLA 2 ) was pivotally involved in the COX-2-mediated generation of PGE 2 in response to a calcium ionophore, as determined by the use of selected PLA 2 inhibitors. PGE 2 biosynthesis elicited by bacterialderived peptides or by phagocytic stimuli acting on cell surface receptors also showed to be dependent on cPLA 2 activity. We then assessed metabolism of unesterified arachidonic acid (AA), and observed that PGE 2 production becomes favored over that of LTB 4 with higher AA concentrations. Withdrawal of calcium prevented the generation of PGE 2 in response to a calcium ionophore but did not affect the up-regulation of COX-2 or its capacity to convert AA, thus limiting its implication at the level of cPLA 2 activation. Of the main eicosanoids produced by neutrophils, only LTB 4 was able to up-regulate COX-2 expression. Finally, the only PGE synthase isoform found in neutrophils is microsomal PGE synthase-1; it co-localized with COX-2 and its expression appeared mainly constitutive. These results highlight key differences in regulatory processes of the 5-LO and COX pathways, and enhance our knowledge at several levels in the PGE 2 biosynthesis in neutrophils.

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“…D'une part, il bloque la libération de l'acide arachi donique de la membrane plasmique et la translocation de [Adénosine] la 5-LO vers la membrane nucléaire, empêchant ainsi la synthèse de LTB 4 [24]. D'autre part, il potentialise l'expression de la COX-2 (transcrit et protéine), in vitro et in vivo [25,26] dans les PN neutrophiles infiltrés dans la poche après une injection de LPS. L'activation du récepteur A 2A peut également inhiber la sécrétion de matrix metalloproteinases (MMP), protéines qui participent à la dégradation matricielle, par exemple MMP9 [29].…”

Section: Polynucléaires Neutrophiles Et Résolution Du Processus Inflaunclassified

Le neutrophile : ennemi ou ami ?

Dumas

Pouliot

2009

Med Sci (Paris)

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Les polynucléaires neutrophiles (PN) sont des agents de premier plan de l'immunité innée, particulièrement lors de la réaction inflammatoire ; ils sont souvent les premiers leucocytes à migrer en grand nombre vers le site enflammé. La réaction inflammatoire est le plus souvent protectrice car elle participe à la défense naturelle de l'organisme et à la réparation des tissus lésés. Malheureusement, si elle est inadaptée ou mal régulée, l'inflammation peut devenir nocive. Ainsi le neutrophile est mis en cause dans la pathogenèse de nombreuses maladies inflammatoires chroniques, comme la polyarthrite rhumatoïde et, en particulier, pour les altérations qu'il cause aux tissus et la dégradation des articulations qui en résulte. Les traitements anti-inflammatoires classiques parviennent à atténuer les symptômes de l'inflammation comme la fièvre, la douleur et l'enflure mais aucun ne permet la guérison. Plusieurs indices suggèrent qu'ils n'empêchent pas l'action destructrice des neutrophiles et pourraient même aggraver la progression des dommages. De meilleures stratégies pourraient consister à augmenter l'efficacité des systèmes de régulation endogènes à l'origine de la sécrétion de molécules anti-inflammatoires. Après un bref rappel des fonctions pro-inflammatoires du neutrophile, cet article mettra l'accent sur les capacités qu'ont ces cellules d'arrêter le processus d'inflammation et l'état de la recherche sur les mécanismes en cause.Le polynuléaire neutrophile, une première ligne de défense pour l'organisme Fonctions de base des PN : élimination des agents infectieux L'action anti-infectieuse du neutrophile repose sur ses capacités de migration transendothéliale, de phagocytose, « d'explosion oxydative » et de dégranulation [1]. De manière physiologique, les PN transitent dans la circulation sanguine en « roulant » sur les cellules endothéliales de la paroi vasculaire (processus de rolling). En réponse à la détection de produits bactériens (peptides formylés, lipopolysaccharides) ou sous l'influence de molécules attractives [leucotriène (LT)B 4 , la chimiokine CXCL8 ou IL(interleukine)-8, fragments du complément, etc.], le PN exprime à sa surface des molécules d'adhé-rence qui vont lui permettre de traverser la paroi endothéliale et de migrer vers le site enflammé. Il reconnaît spécifiquement des motifs présents à la surface des micro-organismes (bactéries, virus), ce qui déclenche leur phagocytose. La dégradation des pathogènes ainsi ingérés s'effectue par deux mécanismes concomitants : la production de formes réactives de l'oxygène (ROS : reactive oxygen species) par la NADPH oxydase et la libé-ration, par les granules des PN, de protéines enzymatiques (myéloperoxydase, élastases, lysosyme, gélatinase)

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Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

Cited by 50 publications

References 60 publications

Estrogen Signaling through the G Protein–Coupled Estrogen Receptor Regulates Granulocyte Activation in Fish

Estrogen Signaling through the G Protein–Coupled Estrogen Receptor Regulates Granulocyte Activation in Fish

Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils

Le neutrophile : ennemi ou ami ?

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