Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells

International Journal of Molecular Sciences

JuanC. Cancino-Diaz¹  Sandra Rodríguez-Martínez¹  MarioE. Cancino-Diaz¹  DianaM. Morales-Prieto²  Tanja Groten²  RodolfoR. Favaro²  JoséM. Murrieta-Coxca²  HebaM. El-Shorafa²  UdoR. Markert²  RubyN. Gutiérrez-Samudio² 

[1] Departamento de Inmunología y Microbiología, Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Mexico City 11340, Mexico;Placenta Lab, Department of Obstetrics, University Hospital Jena, 07740 Jena, Germany;

关键词: pregnancy;    trophoblast;    IL-36 cytokines;    migration;    angiogenesis;    microRNAs;   

DOI  :  10.3390/ijms22010285

来源: DOAJ

【 摘 要 】

IL-36 cytokines (the agonists IL-36α, IL-36β, IL-36γ, and the antagonist IL-36Ra) are expressed in the mouse uterus and associated with maternal immune response during pregnancy. Here, we characterize the expression of IL-36 members in human primary trophoblast cells (PTC) and trophoblastic cell lines (HTR-8/SVneo and JEG-3) and upon treatment with bacterial and viral components. Effects of recombinant IL-36 on the migration capacity of trophoblastic cells, their ability to interact with endothelial cells and the induction of angiogenic factors and miRNAs (angiomiRNAs) were examined. Constitutive protein expression of IL-36 (α, β, and γ) and their receptor (IL-36R) was found in all cell types. In PTC, transcripts for all IL-36 subtypes were found, whereas in trophoblastic cell lines only for IL36G and IL36RN. A synthetic analog of double-stranded RNA (poly I:C) and lipopolysaccharide (LPS) induced the expression of IL-36 members in a cell-specific and time-dependent manner. In HTR-8/SVneo cells, IL-36 cytokines increased cell migration and their capacity to interact with endothelial cells. VEGFA and PGF mRNA and protein, as well as the angiomiRNAs miR-146a-3p and miR-141-5p were upregulated as IL-36 response in PTC and HTR-8/SVneo cells. In conclusion, IL-36 cytokines are modulated by microbial components and regulate trophoblast migration and interaction with endothelial cells. Therefore, a fundamental role of these cytokines in the placentation process and in response to infections may be expected.

【 授权许可】

Unknown