Toll-Like Receptors in Innate Immunity: Role of Bacterial Endotoxin and Toll-Like Receptor 4 in Endometrium and Endometriosis

Khan, Khaleque Newaz; Kitajima, Michio; Hiraki, Koichi; Fujishita, Akira; Sekine, Ichiro; Ishimaru, Tadayuki; Masuzaki, Hiroaki

doi:10.1159/000212061

Cited by 79 publications

(74 citation statements)

References 102 publications

(100 reference statements)

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“…As demonstrated in previous work, women with endometriosis exhibit altered or reduced innate and even adaptive immunity (Dmowski et al, 1981;Ota and Igarashi, 1993;Chiang and Hill, 1997;Khan et al, 2009). Additional studies suggest an autoimmune component to endometriosis (Eisenberg et al, 2012).…”

Section: Discussionsupporting

confidence: 68%

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

Kondova¹,

Braskamp²,

Heidt³

et al. 2017

Primate Biol.

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Abstract. Endometriosis is a poorly understood common debilitating women's reproductive disorder resulting from proliferative and ectopic endometrial tissue associated with variable clinical symptoms including dysmenorrhea (painful menstrual periods), dyspareunia (pain on intercourse), female infertility, and an increased risk of malignant transformation. The rhesus macaque (Macaca mulatta) develops a spontaneous endometriosis that is very similar to that seen in women. We hypothesized that specific major histocompatibility complex (MHC) alleles may contribute to the pathogenesis of endometriosis. As part of a collaboration between the Biomedical Primate Research Centre (BPRC) in the Netherlands and the New England Primate Research Center (NEPRC) in the United States, we analyzed DNA sequences of MHC class I (Macaca mulatta, Mamu-A1) and class II (Mamu-DRB) alleles from rhesus macaques with endometriosis and compared the allele frequencies with those of age-matched healthy macaques. We demonstrate that two MHC class I alleles are overrepresented in diseased macaques compared to controls: Mamu-A1*001, 33.3 % in BPRC animals with endometriosis vs. 11.6 % in healthy macaques (p = 0.007), and Mamu-A1*007, 21.9 % NEPRC rhesus macaques vs. 6.7 %, (p = 0.003). We provide evidence that select MHC class I alleles are associated with endometriosis in rhesus macaques and suggest that the disease pathogenesis contribution of MHC class I warrants further research.

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Section: Discussionsupporting

confidence: 68%

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

Kondova¹,

Braskamp²,

Heidt³

et al. 2017

Primate Biol.

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“…LPS can be transferred to cluster of differentiation 14 (CD14) by LPS-binding protein (LBP) and is recognized by Toll-like receptor 4 (TLR4) on the cell surface (Shimada et al, 2005;Khan et al, 2009;Wu et al, 2016). The interaction between LPS and TLR4 results in the activation of intracellular signaling through myeloid differentiation factor 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF) pathways, leading to the activation of major mitogen-activated protein kinases (MAPKs) and translocation of nuclear transcription factor-κB (NF-κB) (Sheldon and Roberts, 2010;Kawai and Akira, 2011;Huang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Punicalagin protects bovine endometrial epithelial cells against lipopolysaccharide-induced inflammatory injury

Lyu

Chen

Wang

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:Objective: Bovine endometritis is one of the most common reproductive disorders in cattle. The aim of this study was to investigate the anti-inflammation potential of punicalagin in lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (bEECs) and to uncover the underlying mechanisms. Methods: bEECs were stimulated with different concentrations (1, 10, 30, 50, and 100 μg/ml) of LPS for 3, 6, 9, 12, and 18 h. MTT assay was used to assess cell viability and to identify the conditions for inflammatory injury and effective concentrations of punicalagin. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess gene expression of pro-inflammatory cytokines. Western blotting was used to assess levels of inflammation-related proteins. Results: Treatment of bEECs with 30 µg/ml LPS for 12 h induced cell injury and reduced cell viability. Punicalagin (5, 10, or 20 µg/ml) pretreatment significantly decreased LPS-induced productions of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) in bEECs. Molecular research showed that punicalagin inhibited the activation of the upstream mediator nuclear factor-κB (NF-κB) by suppressing the production of inhibitor κBα (IκBα) and phosphorylation of p65. Results also indicated that punicalagin can suppress the phosphorylation of mitogen-activated protein kinases (MAPKs) including p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Conclusions: Punicalagin may attenuate LPS-induced inflammatory injury and provide a potential option for the treatment of dairy cows with Escherichia coli endometritis.

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“…TLR4 plays a very important role in triggering innate immunity and initiating a cascade of pro-inflammatory events through binding pathogenassociated molecules that may drive either from bacteria (such as lipopolysaccharide, LPS), viruses or fungi [4][5][6]. Recently, evidence for TLR4 expression in endothelial cell, monocyte and macrophage has been shown [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 is up-regulated by mTOR activation during THP-1 macrophage foam cells formation

Kang

Xue

et al. 2011

ABBS

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Macrophage foam cells formation is the most important process in atherosclerotic plaque formation and development. Toll-like receptor 4 (TLR4) is one of the important innate immune sensors of endogenous damage signals and crucial for regulating inflammation. Growing evidence indicates that TLR4 plays a very important role in macrophage foam cells formation. However, the underlying mechanisms regulating TLR4 expression in macrophage are not fully understood. In this study, we induced THP-1 macrophage foam cells formation with oxidative modified low-density lipoprotein (ox-LDL). We observed that TLR4 mRNA and protein expression were markedly up-regulated, and the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream target p70S6K were promoted during foam cells formation. The mTOR inhibitor rapamycin blocked mTOR phosphorylation and inhibited TLR4 expression induced by ox-LDL. Silencing mTOR, rictor or raptor protein expression by small interfering RNA, also inhibited the up-regulation of TLR4 expression, respectively. Inhibition of mTOR with rapamycin reversed the down-regulation of cellular lipid efflux mediator ABCA1, which resulted from the activation of TLR4 by ligands. These data suggested that TRL4 expression was up-regulated by a mechanism dependent on mTOR signal pathway activation during THP-1 macrophage foam cells formation. Inhibition of ox-LDL induced mTOR activation reduced TLR4 expression, and improved the impaired lipid efflux.

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Toll-Like Receptors in Innate Immunity: Role of Bacterial Endotoxin and Toll-Like Receptor 4 in Endometrium and Endometriosis

Cited by 79 publications

References 102 publications

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

Punicalagin protects bovine endometrial epithelial cells against lipopolysaccharide-induced inflammatory injury

Toll-like receptor 4 is up-regulated by mTOR activation during THP-1 macrophage foam cells formation

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