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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01030

LPS induces preeclampsia-like phenotype in rats and HTR8/SVneo cells dysfunction through TLR4/p38 MAPK pathway

minghua Fan1, Xiaobing Li2, Xiaolin Gao1, Lihua Dong1, Gang Xin1, Liqun Chen3,  Jianqing Qiu1* and Yongping Xu1*
  • 1Department of Obstetrics and Gynecology, Second Hospital of Shandong University, China
  • 2Shandong Academy of Medical Sciences (SDAMS), China
  • 3Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, China

Accumulating evidence has shown that preeclampsia (PE) was associated with an aberrant maternal-fetal inflammatory response. In the present study, we first found that in human PE placentas levels of Toll-like receptor 4 (TLR4), phosphorylated p38 MAPK (p-p38) and inflammatory cytokines IL-6 and MCP-1 were significantly upregulated. Next, we demonstrated a notable increase in systolic blood pressure (SBP) and proteinuria in lipopolysaccharide (LPS)-treated pregnant rats; and concomitant high levels of TLR4 and p-p38 in these PE-like rat placentas, which led to aberrant overexpression of both IL-6 and MCP-1, as well as deficient trophoblast invasion and spiral artery (SA) remodeling; and these abnormalities were ameliorated by SB203580, a reported inhibitor of p38. In vitro we further confirmed that LPS triggered the activation of TLR4/p38 signaling pathway, which promoted trophoblast apoptosis and damaged trophoblastic invasion via downstream effectors IL-6 and MCP-1; these mutations were rectified by silencing this signaling pathway. These findings elaborated potential mechanisms that aberrant TLR4/p38 signaling might contribute to PE and LPS-induced PE-like symptom by damaging trophoblast invasion and SA remodeling via activating inflammatory cytokines including IL-6 and MCP-1.

Keywords: Preeclampsia, lipopolysaccharide, TLR4, p38 MAPK, Spiral artery, Inflammation

Received: 12 Apr 2019; Accepted: 25 Jul 2019.

Copyright: © 2019 Fan, Li, Gao, Dong, Xin, Chen, Qiu and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jianqing Qiu, Department of Obstetrics and Gynecology, Second Hospital of Shandong University, Jinan, Shandong Province, China,
Prof. Yongping Xu, Department of Obstetrics and Gynecology, Second Hospital of Shandong University, Jinan, Shandong Province, China,