Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation

Cells

Xiang-Yang Ye¹  Paul Sagot²  Fabrice Neiers³  Marc Bardou³  Marina Barrichon⁴  Tarik Hadi⁴  Maeva Wendremaire⁴  Hang Zhang⁴  Tatiana E. Lopez⁴  Carmen Garrido⁴  Frédéric Lirussi⁴ 

[1]School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China

[2]Service de Gynécologie-Obstétrique, Centre Hospitalo-Universitaire Dijon, F-21000 Dijon, France

[3]UFR des Sciences de Santé, Université Bourgogne Franche-Comté, F-25000 Besançon, France

[4]UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France

关键词: leptin;    differentiation;    labour;    macrophage;    myometrium;    oxidative stress;   

DOI  :  10.3390/cells11060954

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown