title: Interleukin 10 deficiency exacerbates toll-like receptor 3-induced preeclampsia-like symptoms in mice.
abstract: Preeclampsia may result from overactivation of the maternal immune system and is characterized by endothelial dysfunction and excessive inflammation. Given the importance of maternal immune system regulation and anti-inflammatory cytokines in normotensive pregnancies, we hypothesized that maternal immune system activation via Toll-like receptor 3 during pregnancy would cause preeclampsia-like symptoms in mice, which would be made worse by deficiency of the anti-inflammatory cytokine interleukin 10. The Toll-like receptor 3 agonist polyinosine-polycytidylic acid (poly I:C) caused hypertension, endothelial dysfunction, and proteinuria in mice only when pregnant. In the absence of poly I:C, pregnant interleukin 10 knockout mice exhibited a significant increase in systolic blood pressure, endothelial dysfunction, and serum proinflammatory cytokines, as well as aortic and placental platelet-endothelial cell adhesion molecule expression compared with pregnant wild-type mice. Deficiency of interleukin 10 further augmented these measures in poly I:C-treated pregnant mice. In addition, sera from poly I:C-treated pregnant wild-type mice significantly decreased relaxation responses and increased platelet-endothelial cell adhesion molecule expression in isolated aortas from nonpregnant wild-type mice, and these effects were augmented by sera from poly I:C-treated interleukin 10 knockout mice. Coincubation with recombinant interleukin 10 normalized relaxation responses and platelet-endothelial cell adhesion molecule expression in all of the groups. Collectively, Toll-like receptor 3 activation during pregnancy causes preeclampsia-like symptoms, which are exacerbated by the absence of interleukin 10. Exogenous interleukin 10 treatment had beneficial effects on endothelial function and may be beneficial in women with preeclampsia.
authors.affiliation: Department of Internal Medicine, Texas A&M Health Science Center/Scott & White Memorial Hospital, 702 SW HK Dodgen Loop, Temple, TX 76504, USA.
authors.forename: Piyali
authors.initials: P
authors.lastname: Chatterjee
authors.forename: Valorie L
authors.initials: VL
authors.lastname: Chiasson
authors.forename: Shelley E
authors.initials: SE
authors.lastname: Kopriva
authors.forename: Kristina J
authors.initials: KJ
authors.lastname: Young
authors.forename: Victor
authors.initials: V
authors.lastname: Chatterjee
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jones
authors.forename: Brett M
authors.initials: BM
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D011247:Pregnancy; D011507:Proteinuria / Q000652:urine; D011994:Recombinant Proteins / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016207:Cytokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D016753:Interleukin-10; D011070:Poly I-C