title: Placental Toll-like receptor 3 and Toll-like receptor 7/8 activation contributes to preeclampsia in humans and mice.
abstract: Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome characterized by excessive maternal immune system activation, inflammation, and endothelial dysfunction. Toll-like receptor (TLR) 3 activation by double-stranded RNA (dsRNA) and TLR7/8 activation by single-stranded RNA (ssRNA) expressed by viruses and/or released from necrotic cells initiates a pro-inflammatory immune response; however it is unknown whether viral/endogenous RNA is a key initiating signal that contributes to the development of PE. We hypothesized that TLR3/7/8 activation will be evident in placentas of women with PE, and sufficient to induce PE-like symptoms in mice. Placental immunoreactivity and mRNA levels of TLR3, TLR7, and TLR8 were increased significantly in women with PE compared to normotensive women. Treatment of human trophoblasts with the TLR3 agonist polyinosine-polycytidylic acid (poly I:C), the TLR7-specific agonist imiquimod (R-837), or the TLR7/8 agonist CLO97 significantly increased TLR3/7/8 levels. Treatment of mice with poly I:C, R-837, or CLO97 caused pregnancy-dependent hypertension, endothelial dysfunction, splenomegaly, and placental inflammation. These data demonstrate that RNA-mediated activation of TLR3 and TLR7/8 plays a key role in the development of PE.
authors: Department of Internal Medicine, Texas A&M Health Science Center/Scott and White Memorial Hospital, Temple, Texas, United States of America.
authors: Piyali
authors: P
authors: Chatterjee
authors: Laura E
authors: LE
authors: Weaver
authors: Karen M
authors: KM
authors: Doersch
authors: Shelley E
authors: SE
authors: Kopriva
authors: Valorie L
authors: VL
authors: Chiasson
authors: Samantha J
authors: SJ
authors: Allen
authors: Ajay M
authors: AM
authors: Narayanan
authors: Kristina J
authors: KJ
authors: Young
authors: Kathleen A
authors: KA
authors: Jones
authors: Thomas J
authors: TJ
authors: Kuehl
authors: Brett M
authors: BM
authors: Mitchell
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors