Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPHoxidase activity and induces catalase expression via PPAR gamma activation
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Titre | Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPHoxidase activity and induces catalase expression via PPAR gamma activation |
Type de publication | Journal Article |
Year of Publication | 2017 |
Auteurs | Hadi T, Douhard R, Dias AMM, Wendremaire M, Pezze M, Bardou M, Sagot P, Garrido C, Lirussi F |
Journal | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH |
Volume | 1864 |
Pagination | 1769-1784 |
Date Published | OCT |
Type of Article | Article |
ISSN | 0167-4889 |
Mots-clés | beta3 adrenergic receptor, macrophage, PPAR gamma, preterm labor, ROS |
Résumé | The beta3 adrenergic receptor (beta 3-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 beta 3-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 beta 3-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 beta 3-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 PPAR gamma. These results suggest that beta 3-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. |
DOI | 10.1016/j.bbamcr.2017.07.003 |