Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPHoxidase activity and induces catalase expression via PPARγ activation

Tarik Hadi 1, 2 Romain Douhard 3 Alexandre M Dias 3 Maeva Wendremaire 3, 4 Maria Pezzè 3 Marc Bardou 5, 3 Paul Sagot 6 Carmen Garrido 3, 7 Frédéric Lirussi 3, 4, *
* Auteur correspondant
1 Institut National de la Santé et de la Recherche Médicale
2 NYU Langone Medical Center - New York University Langone Medical Center
3 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
4 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
5 CIC-P803 - Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie
6 Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon]
7 Département d'oncologie médicale [Centre Georges-François Leclerc]
Abstract : The beta3 adrenergic receptor (β3-AR) stimulation plays a protective role against preterm labor by blocking myometrial contraction, cytokine production, remodeling and apoptosis. We previously demonstrated that macrophage-induced ROS production in the myometrium was a key element leading to the induction of all these labor-associated features. We thus aimed to investigate if the β3-AR could be expressed in human macrophages and could trigger its protective role in the myometrium by directly inhibiting ROS production. Using lipopolysaccharide (LPS)-stimulated myometrial samples and cell co-culture experiments, we demonstrated that β3-AR stimulation inhibits the activation of the NADPH oxidase, leading to the subsequent inhibition of ROS production by macrophages. This antioxidant effect was associated with a potent anti-inflammatory response in macrophages. Furthermore, we observed that β3-AR leads to the expression of catalase not only in macrophages but also in myometrial cells, thereby preventing the transactivation of myometrial cells by hydrogen peroxide. Pharmacological experiments allowed us to demonstrate that these effects were driven by an Erk1/2-mediated activation of the antioxidant transcription factor PPARγ. These results suggest that β3-AR protective effects in the myometrium could be due to its dual antioxidant properties. Further, the effects observed in a macrophage could highlight new applications in chronic inflammatory diseases.
Keywords : Macrophage PPARγ Preterm labor ROS beta3 adrenergic receptor
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Soumis le : lundi 28 août 2017 - 16:33:54
Dernière modification le : vendredi 8 juin 2018 - 14:50:25

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Tarik Hadi, Romain Douhard, Alexandre M Dias, Maeva Wendremaire, Maria Pezzè, et al.. Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPHoxidase activity and induces catalase expression via PPARγ activation. BBA - Biochimica et Biophysica Acta, Elsevier, 2017, 1864 (10), pp.1769-1784. ⟨10.1016/j.bbamcr.2017.07.003⟩. ⟨hal-01578123⟩

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