Rosiglitazone alleviates LPS-induced endometritis via suppression of TLR4-mediated NF-κB activation

Hongchu Bao; Jianxiang Cong; Qinglan Qu; Shunzhi He; Dongmei Zhao; Huishan Zhao; Shuyuan Yin; Ding Ma

doi:10.1371/journal.pone.0280372

Rosiglitazone alleviates LPS-induced endometritis via suppression of TLR4-mediated NF-κB activation

PLoS One. 2024 Mar 28;19(3):e0280372. doi: 10.1371/journal.pone.0280372. eCollection 2024.

Authors

Hongchu Bao^{1

2}, Jianxiang Cong^{1

2}, Qinglan Qu^{1

2}, Shunzhi He^{1

2}, Dongmei Zhao^{1

2}, Huishan Zhao^{1

2}, Shuyuan Yin^{1

2}, Ding Ma^{1

2}

Affiliations

¹ Reproductive Medicine Centre, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
² Shandong Provincial Key Medical and Health Laboratory of Reproductive Health and Genetics (Yantai Yuhuangding Hospital), Yantai, China.

Abstract

Objective: The aim of this study was to investigate the anti-inflammatory effect of Rosiglitazone (RGZ) on lipopolysaccharide (LPS) -induced Endometritis and explore its possible mechanism.

Methods: The preventive and therapeutic effects of RGZ on Endometritis were studied in vivo and in vitro. A total of 40 female C57BL/6 mice were randomly divided into the following 4 groups: RGZ+LPS, RGZ control, LPS and DMSO control. The mice uterine tissue sections were performed with HE and immunohistochemical staining. Human endometrial stromal cells (HESCs) were cultured, and different concentrations of LPS stimulation groups and RGZ and/or a TLR4 signaling inhibitor TAK-242 pretreatment +LPS groups were established to further elucidate the underlying mechanisms of this protective effect of RGZ.

Results: The HE results in mice showed that RGZ+LPS group had less tissue loss than LPS group. Immunohistochemical staining (IHC) results showed that the expression of TLR4 after RGZ treatment was significantly lower than that in LPS group. These findings suggested that RGZ effectively improves the pathological changes associated with LPS-induced endometritis by inhibiting TLR4. Reverse transcription-polymerase chain reaction and western blot analysis demonstrated that RGZ pretreatment suppresses the expression of Toll-like receptor 4 (TLR4) and its downstream activation of nuclear factor-κB (NF-κB). In vitro, RGZ inhibited LPS-stimulated expression of proinflammatory cytokines in a dose-dependent manner and also downregulated LPS induced toll-like receptor 4 (TLR4) expression and inhibited phosphorylation of LPS-induced nuclear transcription factor-kappa B (NF-κB) P65 protein.

Conclusions: These results suggest that RGZ may inhibit LPS-induced endometritis through the TLR4-mediated NF-κB pathway.

Copyright: © 2024 Bao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Animals
Endometritis* / chemically induced
Endometritis* / drug therapy
Female
Humans
Lipopolysaccharides / toxicity
Mice
Mice, Inbred C57BL
NF-kappa B* / metabolism
Rosiglitazone / pharmacology
Rosiglitazone / therapeutic use
Signal Transduction
Toll-Like Receptor 4 / metabolism

Substances

NF-kappa B
Lipopolysaccharides
Toll-Like Receptor 4
Rosiglitazone
TLR4 protein, human

Grants and funding

The study was supported by Shandong Medical and Health Science and Technology Development Project (No.202005030944). The study was supported by Shandong Medical and Health Science and Technology Development Project (No.202005030944). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.