LPS Induces Preeclampsia-Like Phenotype in Rats and HTR8/SVneo Cells Dysfunction Through TLR4/p38 MAPK Pathway

Overview

Journal Front Physiol

Date 2019 Sep 12

PMID 31507429

Citations 29

Authors

Minghua Fan

Xiaobing Li

Xiaolin Gao

Lihua Dong

Gang Xin

Liqun Chen

Jianqing Qiu

Yongping Xu

Affiliations

Soon will be listed here.

Abstract

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 mitogen-activated protein kinase (p-p38 MAPK) 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. we further confirmed that LPS triggered the activation of TLR4/p38 signaling pathway, which promoted trophoblast apoptosis and damaged trophoblastic invasion 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 activating inflammatory cytokines including IL-6 and MCP-1.

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