Regulatory roles of PGE2 in LPS-induced tissue damage in bovine endometrial explants

Deng, Yang; Liu, Bo; Mao, Wei; Shen, Yuan; Fu, Changqi; Gao, Long; Zhang, Shuangyi; Wu, Jindi; Li, Qianru; Li, Tingting; Liu, Kun; Cao, Jinshan

doi:10.1016/j.ejphar.2019.03.044

Cited by 18 publications

(15 citation statements)

References 46 publications

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“…terminal synthase, which is usually coupled with COX-2 to mediate the production of PGE2 in inflammatory states (Deng et al, 2019;Thoren & Jakobsson, 2000;Uematsu, Matsumoto, Takeda, & Akira, 2002), has gained considerable attention as a preferable target for new generation of antipyretic and analgesic drugs (Bergqvist, Morgenstern, & Jakobsson, 2019;Yang & Chen, 2016). It has been reported that, unlike COX-2 selective inhibitors, deletion of mPGES-1 in mice is protective to inflammatory vascular diseases, for example, retards atherogenesis (Wang et al, 2006), suppresses abdominal aortic aneurysm formation (Wang et al, 2008a), limits post-injury neointima hyperplasia (Wang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Microsomal Prostaglandin E₂ Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice

Guo

Wang

et al. 2020

J Pharmacol Exp Ther

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Deletion of microsomal PGE2 synthase-1 (mPGES-1) inhibits inflammation and protects against atherosclerotic vascular diseases, but displayed variable influence on pathological cardiac remodeling. Overactivation of β-adrenergic receptors (β-ARs) causes heart dysfunction and cardiac remodeling, while the role of mPGES-1 in β-ARs induced cardiac remodeling is unknown. Here we addressed this question using mPGES-1 knockout mice, and subjecting them to isoproterenol, a synthetic nonselective agonist for β-ARs, at 5mg/kg/day or 15mg/kg/day to induce different degrees of cardiac remodeling in vivo. Cardiac structure and function were assessed by echocardiography 24 hours after the last of seven consecutive daily injections of isoproterenol, and cardiac fibrosis was examined by Masson trichrome stain in morphology and by real-time PCR for the expression of fibrosis related genes. The results showed that deletion of mPGES-1 had no significant effect on isoproterenol-induced cardiac dysfunction or hypertrophy. However, the cardiac fibrosis was dramatically attenuated in the mPGES-1 knockout mice after either low dose or high dose isoproterenol exposure. Furthermore, in vitro study revealed that overexpression of mPGES-1 in cultured cardiac fibroblasts increased isoproterenol induced fibrosis, while knocking-down mPGES-1 in cardiac myocytes decreased the fibrogenesis of fibroblasts. In conclusion, mPGES-1 deletion protects against isoproterenol-induced cardiac fibrosis in mice, and targeting mPGES-1 may represent a novel strategy to attenuate pathological cardiac fibrosis, induced by β-ARs agonists.

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Section: Introductionmentioning

confidence: 99%

Microsomal Prostaglandin E₂ Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice

Guo

Wang

et al. 2020

J Pharmacol Exp Ther

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“…This could result from the animal and in vivo bacterial status [33] during the 56 days of the observation period. Previously, it has been well-established that the overexpression of COX-2 and PGE2 contributes to pathogenesis in a number of bacterial, fungal, and viral infections, such as Streptococcus suis [34], Escherichia coli [35,36], Chlamydia trachomatis [37], Candida albicans [38], H1N1 influenza virus [39], and Theiler's murine encephalomyelitis virus [40]. Correspondingly, the bacterial load and abnormality levels in M. bovis-infected mice were higher than those in BCG-infected mice.…”

Section: Differences In Differentiation Of Treg and Pathogenic Th17 Cmentioning

confidence: 99%

“…The mycobacterial burden and histopathological lesions in the lung and spleen tissues of infected mice were used to comparatively assess the virulence of M. bovis and BCG in mice. The strains cultured to logarithmic phase were injected into mice by the tail vein, consisting of 2 × 10 5 CFU per mouse, and mice were then respectively sacrificed on 1,4,7,14,21,28,35,49, and 56 days postinfection. In the spleens from M. bovis and BCG infection groups, the bacterial load increased slowly after the first day, maintained a high level for 14 days, and then began to decline ( Figure 6A).…”

Section: Higher Bacterial Load and More Severe Tissue Lesions Developmentioning

confidence: 99%

Upregulation of Cytokines and Differentiation of Th17 and Treg by Dendritic Cells: Central Role of Prostaglandin E2 Induced by Mycobacterium bovis

et al. 2020

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Mycobacterium bovis (M. bovis) is a zoonotic pathogen that causes bovine and human tuberculosis. Dendritic cells play a critical role in initiating and regulating immune responses by promoting antigen-specific T-cell activation. Prostaglandin E2 (PGE2)-COX signaling is an important mediator of inflammation and immunity and might be involved in the pathogenesis of M. bovis infection. Therefore, this study aimed to reveal the character of PGE2 in the differentiation of naïve CD4+ T cells induced by infected dendritic cells (DCs). Murine bone marrow-derived DCs were pre-infected with M. bovis and its attenuated strain M. bovis bacillus Calmette-Guérin (BCG). Then, the infected DCs were co-cultured with naïve CD4+ T cells with or without the cyclooxygenase (COX) inhibitor indomethacin. Quantitative RT-PCR analysis and protein detection showed that PGE2/COX-2 signaling was activated, shown by the upregulation of PGE2 production as well as COX-2 and microsomal PGE2 synthase (mPGES1) transcription in DCs specifically induced by M. bovis and BCG infection. The further co-culture of infected DCs with naïve CD4+ T cells enhanced the generation of inflammatory cytokines IL-17 and IL-23, while indomethacin suppressed their production. Following this, the differentiation of regulatory T cells (Treg) and Th17 cell subsets was significantly induced by the infected DCs rather than uninfected DCs. Meanwhile, M. bovis infection stimulated significantly higher levels of IL-17 and IL-23 and the differentiation of Treg and Th17 cell subsets, while BCG infection led to higher levels of TNF-α and IL-12, but lower proportions of Treg and Th17 cells. In mice, M. bovis infection generated more bacterial load and severe abnormalities in spleens and lungs, as well as higher levels of COX-2, mPGE2 expression, Treg and Th17 cell subsets than BCG infection. In conclusion, PGE2/COX-2 signaling was activated in DCs by M. bovis infection and regulated differentiation of Treg and Th17 cell subsets through the crosstalk between DCs and naive T cells under the cytokine atmosphere of IL-17 and IL-23, which might contribute to M. bovis pathogenesis in mice.

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“…In addition, a previous study showed also that LPS treated bovine endometrial explants in vitro, which resulted in luminal epithelial cell shedding and damage. Many bacteria and toxins start attacking BESCs because of losing epithelium, which stimulates Toll-like receptors (TLRs) on BESCs and causes upregulated expression of cytokines (12). BESCs have a more positive role in resisting pyolysin-mediated cytolysis compared with BEECs and are more accessible to the vascular system and mononuclear cells; thus, the effect of stromal cytokines is more significant (3,(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Transcriptomic Changes in Bovine Endometrial Stromal Cells Treated With Lipopolysaccharide

Ding

Deng

et al. 2020

Front. Vet. Sci.

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Endometritis adversely affects the ability of cattle to reproduce and significantly reduces milk production. The is mainly composed of epithelial and stromal cells, and they produce the first immune response to invading pathogens. However, most of the epithelial cells are disrupted, and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. Many bacteria and toxins start attacking stromal cell due to loss of epithelium, which stimulates Toll-like receptor (TLRs) on stromal cells and causes upregulated expression of cytokines. Understanding the genome-wide characterization of bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine endometrial stromal cells (BESCs) treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing. Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in the LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted P < 0.05 by DESeq. Gene Ontology (GO) enrichment analysis revealed that DEGs were most enriched in interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in the TNF signaling pathway, Toll-like receptor signaling pathway, cytokine–cytokine receptor interaction, NF-κB signaling pathway, and chemokine signaling pathway. The results of this study unraveled BESCs affected with LPS transcriptome profile alterations, which may have a significant effect on treatment inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.

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Regulatory roles of PGE2 in LPS-induced tissue damage in bovine endometrial explants

Cited by 18 publications

References 46 publications

Microsomal Prostaglandin E₂ Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice

Microsomal Prostaglandin E₂ Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice

Upregulation of Cytokines and Differentiation of Th17 and Treg by Dendritic Cells: Central Role of Prostaglandin E2 Induced by Mycobacterium bovis

Analysis of Transcriptomic Changes in Bovine Endometrial Stromal Cells Treated With Lipopolysaccharide

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Regulatory roles of PGE2 in LPS-induced tissue damage in bovine endometrial explants

Cited by 18 publications

References 46 publications

Microsomal Prostaglandin E2 Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice

Microsomal Prostaglandin E2 Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice

Upregulation of Cytokines and Differentiation of Th17 and Treg by Dendritic Cells: Central Role of Prostaglandin E2 Induced by Mycobacterium bovis

Analysis of Transcriptomic Changes in Bovine Endometrial Stromal Cells Treated With Lipopolysaccharide

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Microsomal Prostaglandin E₂ Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice

Microsomal Prostaglandin E₂ Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice