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Article Dans Une Revue Cells Année : 2022

Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation

Xiang-Yang Ye

Résumé

Maternal obesity is associated with a wide spectrum of labour disorders, including preterm birth. Leptin, a pro-inflammatory adipokine and a key factor of obesity, is suspected to play a major role in these disorders. OB-R, its receptor, is expressed on macrophages and myocytes, two cell types critical for labour onset. Macrophages secrete reactive oxygen species/pro-inflammatory cytokines, responsible for myometrial differentiation while myocytes control uterine contractions. In this study, we assessed the effect of leptin on myometrial contraction and differentiation using our validated co-culture model of human primary macrophages and myocytes. We demonstrated that leptin had a different effect on myocytes and macrophages depending on the dose. A low leptin concentration induced a tocolytic effect by preventing myocytes’ contraction, differentiation, and macrophage-induced ROS production. Additionally, leptin led to an increase in HLA-G expression, suggesting that the tocolytic effect of leptin may be driven by HLA-G, a tolerogenic molecule. Finally, we observed that recombinant HLA-G also prevented LPS-induced ROS production by macrophages. Altogether, these data provide a putative molecular mechanism by which leptin may induce immune tolerance and therefore interfere with labour-associated mechanisms. Therefore, HLA-G represents a potential innovative therapeutic target in the pharmacological management of preterm labour.

Dates et versions

hal-03642029 , version 1 (14-04-2022)

Identifiants

Citer

Maeva Wendremaire, Tatiana Lopez, Marina Barrichon, Hang Zhang, Tarik Hadi, et al.. Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation. Cells, 2022, 11 (6), pp.954. ⟨10.3390/cells11060954⟩. ⟨hal-03642029⟩
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