scholarly journals Vitamin D3 Controls TLR4- and TLR2-Mediated Inflammatory Responses of Endometrial Cells

2021 ◽  
pp. 1-10
Author(s):  
Alireza Ghanavatinejad ◽  
Nesa Rashidi ◽  
Mahroo Mirahmadian ◽  
Simin Rezania ◽  
Mahdokht Mosalaei ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Inflammatory Responses ◽  
Female Reproductive Tract ◽  
In Vivo Studies ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Tnf Α ◽  
Tract Infections

<b><i>Objectives:</i></b> Vitamin D has potent immunoregulatory features and modulates innate and adaptive immune responses. There is a significant association between intrauterine infection-associated inflammatory responses and pregnancy complications such as abortion and preterm labor. Here, we investigated how 1,25 (OH)2 D3 could modulate inflammatory responses of endometrial cells. <b><i>Design:</i></b> This is an in vitro experimental study. Endometrial stromal cells (ESCs) and whole endometrial cells (WECs) were collected from 15 apparently normal women, and the immunomodulatory effects of 1,25 (OH)2 D3 on lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated ESCs and WECs were investigated. <b><i>Participants/Materials, Setting, and Methods:</i></b> Women with no history of abortion, infertility, endometriosis, or sign of vaginal infection were enrolled in this study. Endometrial samples were collected by gynecologists using a Pipelle pipette in the proliferative phase of the menstrual cycle. WECs and ESCs were collected and treated with either LPS or LTA. The levels of IL-6, IL-8, and TNF-α in culture supernatants were quantified using the ELISA technique. TLR2, TLR4, and MyD88 expressions were assessed by RT-qPCR. TLR4 expression at the protein level was studied by the Western blot technique. <b><i>Results:</i></b> 1,25 Dihydroxycholecalciferol (1,25 (OH)2 D3) significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pretreatment increased the production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pretreatment markedly reduced LPS-induced TLR4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pretreated with 1,25 (OH)2 D3 before stimulation with LPS. <b><i>Limitations:</i></b> Because of the small size of samples, doing experiments all together on some samples was not feasible. Confirmation of the results obtained here needs well-designed in vivo studies. <b><i>Conclusions:</i></b> 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintaining endometrial immune homeostasis by controlling potentially harmful inflammatory responses associated with female reproductive tract infections.

scholarly journals Vitamin D3 controls TLR4- and TLR2-mediated inflammatory responses of endometrial cells

2019 ◽  
Author(s):  
Alireza Ghanavatinejad ◽  
Nesa Rashidi ◽  
Mahroo Mirahmadian ◽  
Simin Rezania ◽  
Mahdokht Mosalaei ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Vitamin D3 ◽  
Inflammatory Responses ◽  
Female Reproductive Tract ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Tnf Α ◽  
Pre Treatment ◽  
Tract Infections ◽  
Pro Inflammatory Cytokines

Abstract Background: There is a significant association between intrauterine infection-associated inflammatory responses and such pregnancy complications as abortion and preterm labor. Here, we aimed to investigate anti-inflammatory effects of 1,25 (OH)2 D3 on pro-inflammatory cytokines secretion and expression of TLR2, TLR4 and MyD88 in endometrial stromal cells (ESCs) and whole endometrial cells (WECs). Method: WECs were treated with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) and ESCs were treated with LPS. IL-6, IL8 and TNF-α were quantified using ELISA technique. TLR2, TLR4 and MyD88 expression were assessed by RT-qPCR. TLR4 expression at the protein level was studied by Western blot technique. Results: 1,25 (OH)2 D3 significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pre-treatment increased production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pre-treatment markedly reduced LPS-induced TLR-4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pre-treated with 1,25 (OH)2 D3 before stimulation with LPS. Conclusion: 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintenance of endometrial immune homeostasis through controlling potentially harmful inflammatory responses associated with female reproductive tract infections. Key words: Vitamin D3, Endometrium, Inflammation, Toll like receptors, Pro-inflammatory cytokines

scholarly journals WNK1 regulates uterine homeostasis and its ability to support pregnancy

2020 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Tianyuan Wang ◽  
Chou-Long Huang ◽  
San-pin Wu ◽  
Steven Young ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Embryo Implantation ◽  
Ion Homeostasis ◽  
Female Reproductive Tract ◽  
Female Reproduction ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Akt Phosphorylation

AbstractWNK1 is an atypical kinase protein ubiquitously expressed in humans and mice. A mutation in its encoding gene causes hypertension in humans which is associated with abnormal ion homeostasis. Our earlier findings demonstrated that WNK1 is critical for in vitro decidualization in human endometrial stromal cells – pointing towards an unrecognized role of WNK1 in female reproduction. Here, we employed a mouse model with conditional WNK1 ablation from the female reproductive tract to define its in vivo role in uterine biology. Loss of WNK1 altered uterine morphology, causing endometrial epithelial hyperplasia, adenomyosis and a delay in embryo implantation, ultimately resulting in compromised fertility. Combining transcriptomic, proteomic and interactomic analyses revealed a novel regulatory pathway whereby WNK1 represses AKT phosphorylation through the phosphatase PP2A in endometrial cells from both humans and mice. We show that WNK1 interacts with PPP2R1A, an isoform of the PP2A scaffold subunit. This interaction stabilizes the PP2A complex, which then dephosphorylates AKT. Therefore, loss of WNK1 reduced PP2A activity, causing AKT hypersignaling. Using FOXO1 as a readout of AKT activity, we demonstrate that there was escalated FOXO1 phosphorylation and nuclear exclusion, leading to a disruption in the regulation of genes that are crucial for embryo implantation.

scholarly journals Neisseria gonorrhoeaePilus Attenuates Cytokine Response of Human Fallopian Tube Explants

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Luis Velasquez ◽  
Katherine García ◽  
Francisco Morales ◽  
John E. Heckels ◽  
Pedro Orihuela ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Reproductive Tract ◽  
Inflammatory Responses ◽  
Female Reproductive Tract ◽  
Gm Csf ◽  
Human Fallopian Tube ◽  
Tnf Α ◽  
Epithelial Cell Surface ◽  
Mucosal Explants

Background. A role for pilus during attachment ofNeisseria gonorrhoeaeto epithelia of the female reproductive tract is currently assumed. However, Pil−gonococci have been observed during infection of the reproductive tract, which prompted us to examine the effect of pili on the dynamics of infection and the inflammatory responses of mucosal explants of the human Fallopian tube.Methods. Mucosal explants were infected in vitro with Opa negative Pil−and Pil+N. gonorrhoeaestrains.Results. Piliation enhanced gonococcal adherence to the epithelium within 3 h of infection (P<0.05) but thereafter did not offer advantage to gonococci to colonize the epithelial cell surface (P>0.05). No differences were found between the strains in numbers of gonococci inside epithelial cells. Pil−bacteria induced higher levels (P<0.05) of IL-1β, TNF-α, GM-CSF, MCP-1, and MIP-1β than Pil+bacteria. There were no differences between both strains in LOS pattern, and Pil expression did not change after coincubation with mucosal strips.Conclusions. Results show that gonococcal invasion of the human Fallopian tube can occur independently of pilus or Opa expression, and suggest that pilus, by inhibition of several key elements of the initial inflammatory response, facilitates sustained infection of this organ.

scholarly journals Mechanisms of Adiponectin Action in Fertility: An Overview from Gametogenesis to Gestation in Humans and Animal Models in Normal and Pathological Conditions

2019 ◽  
Vol 20 (7) ◽  
pp. 1526 ◽  
Author(s):  
Alix Barbe ◽  
Alice Bongrani ◽  
Namya Mellouk ◽  
Anthony Estienne ◽  
Patrycja Kurowska ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Polycystic Ovary ◽  
Embryo Implantation ◽  
Female Reproductive Tract ◽  
Trophoblast Invasion ◽  
Endometrial Cells ◽  
Foetal Growth ◽  
Foetal Growth Restriction

Adiponectin is the most abundant plasma adipokine. It mainly derives from white adipose tissue and plays a key role in the control of energy metabolism thanks to its insulin-sensitising, anti-inflammatory, and antiatherogenic properties. In vitro and in vivo evidence shows that adiponectin could also be one of the hormones controlling the interaction between energy balance and fertility in several species, including humans. Indeed, its two receptors—AdipoR1 and AdipoR2—are expressed in hypothalamic–pituitary–gonadal axis and their activation regulates Kiss, GnRH and gonadotropin expression and/or secretion. In male gonads, adiponectin modulates several functions of both somatic and germ cells, such as steroidogenesis, proliferation, apoptosis, and oxidative stress. In females, it controls steroidogenesis of ovarian granulosa and theca cells, oocyte maturation, and embryo development. Adiponectin receptors were also found in placental and endometrial cells, suggesting that this adipokine might play a crucial role in embryo implantation, trophoblast invasion and foetal growth. The aim of this review is to characterise adiponectin expression and its mechanism of action in male and female reproductive tract. Further, since features of metabolic syndrome are associated with some reproductive diseases, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia, endometriosis, foetal growth restriction and ovarian and endometrial cancers, evidence regarding the emerging role of adiponectin in these disorders is also discussed.

scholarly journals Exosomes Transport Anti-Human Immunodeficiency Virus Factors from Human Cervical Epithelial Cells to Macrophages

2021 ◽  
pp. 1-11
Author(s):  
Xi-Qiu Xu ◽  
Biao Zhang ◽  
Le Guo ◽  
Yu Liu ◽  
Feng-Zhen Meng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Hiv Infection ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Female Reproductive Tract ◽  
In Vivo Studies ◽  
Cervical Epithelial Cells ◽  
Anti Hiv

The female reproductive tract (FRT) is a major site of HIV sexual transmission. As the outermost layer of cells in the FRT, the human cervical epithelial cells (HCEs) have direct contact with HIV or infected cells. Our early work showed that supernatant (SN) from TLR3-activated HCEs contain the antiviral factors that could potently inhibit HIV replication in macrophages. However, it remains to be determined how HCEs transport the anti-HIV factors to macrophages. This follow-up study examined the role of exosomes in HCE-mediated anti-HIV activity. We found that TLR3 activation of HCEs resulted in the release of exosomes that contained multiple IFN-stimulated genes (ISGs: <i>ISG56</i>, <i>OAS1</i>, <i>MxA,</i> and <i>Mx2</i>) and the HIV restriction microRNAs (miR-28, miR-29 family members, miR-125b, miR-150, miR-382, miR-223, miR-20a, and miR-198). The depletion of exosomes from SN of TLR3-activated HCEs diminished HCE-mediated anti-HIV activity in macrophages, indicating that HCE-derived exosomes are responsible for transporting the antiviral molecules to macrophages. These in vitro findings suggest a novel antiviral mechanism by which HCEs participate in the FRT innate immunity against HIV infection. Further in vivo studies are necessary in order to develop an exosome-based delivery system for prevention and treatment of HIV infection through sexual transmission.

scholarly journals Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 123
Author(s):  
Natalia K. Kordulewska ◽  
Justyna Topa ◽  
Małgorzata Tańska ◽  
Anna Cieślińska ◽  
Ewa Fiedorowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Reaction ◽  
Wide Spectrum ◽  
Cell Monolayer ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

scholarly journals The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1318
Author(s):  
Tarek Benameur ◽  
Raffaella Soleti ◽  
Chiara Porro
Keyword(s):  
Inflammatory Responses ◽  
Pathological Condition ◽  
Neurological Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
In Vivo Studies ◽  
Innovative Drug ◽  
Chronic Neuroinflammation

Chronic neuroinflammation is a pathological condition of numerous central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and many others. Neuroinflammation is characterized by the microglia activation and concomitant production of pro-inflammatory cytokines leading to an increasing neuronal cell death. The decreased neuroinflammation could be obtained by using natural compounds, including flavonoids known to modulate the inflammatory responses. Among flavonoids, quercetin possess multiple pharmacological applications including anti-inflammatory, antitumoral, antiapoptotic and anti-thrombotic activities, widely demonstrated in both in vitro and in vivo studies. In this review, we describe the recent findings about the neuroprotective action of quercetin by acting with different mechanisms on the microglial cells of CNS. The ability of quercetin to influence microRNA expression represents an interesting skill in the regulation of inflammation, differentiation, proliferation, apoptosis and immune responses. Moreover, in order to enhance quercetin bioavailability and capacity to target the brain, we discuss an innovative drug delivery system. In summary, this review highlighted an important application of quercetin in the modulation of neuroinflammation and prevention of neurological disorders.

scholarly journals Viperin is anti-viral in vitro but is dispensable for restricting dengue virus replication or induction of innate and inflammatory responses in vivo

2021 ◽  
Vol 102 (10) ◽  
Author(s):  
Wisam-Hamzah Al Shujairi ◽  
Luke P. Kris ◽  
Kylie van der Hoek ◽  
Evangeline Cowell ◽  
Gustavo Bracho-Granado ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Denv Infection ◽  
Brain Morphology ◽  
Moderate Increase ◽  
Tnf Α ◽  
Significant Difference

Viperin has antiviral function against many viruses, including dengue virus (DENV), when studied in cells in culture. Here, the antiviral actions of viperin were defined both in vitro and in a mouse in vivo model of DENV infection. Murine embryonic fibroblasts (MEFs) derived from mice lacking viperin (vip−/−) showed enhanced DENV infection, accompanied by increased IFN-β and induction of ISGs; IFIT1 and CXCL-10 but not IRF7, when compared to wild-type (WT) MEFs. In contrast, subcutaneous challenge of immunocompetent WT and vip−/− mice with DENV did not result in enhanced infection. Intracranial infection with DENV resulted in body weight loss and neurological disease with a moderate increase in mortality in vip−/− compared with WT mice, although this was not accompanied by altered brain morphology, immune cell infiltration or DENV RNA level in the brain. Similarly, DENV induction of IFN-β, IFIT1, CXCL-10, IRF7 and TNF-α was not significantly different in WT and vip−/− mouse brain, although there was a modest but significant increase in DENV induction of IL-6 and IfI27la in the absence of viperin. NanoString nCounter analysis confirmed no significant difference in induction of a panel of inflammatory genes in WT compared to vip−/− DENV-infected mouse brains. Further, polyI:C stimulation of bone marrow-derived macrophages (BMDMs) induced TNF-α, IFN-β, IL-6 and Nos-2, but responses were not different in BMDMs generated from WT or vip−/− mice. Thus, while there is significant evidence of anti-DENV actions of viperin in some cell types in vitro, for DENV infection in vivo a lack of viperin does not affect systemic or brain susceptibility to DENV or induction of innate and inflammatory responses.

Differential modulation of complement factor H and C3 expression by TNF-α in the rat. In vitro and in vivo studies

1992 ◽  
Vol 29 (7-8) ◽  
pp. 983-988 ◽  
Author(s):  
Nathalie Julen ◽  
Christian Davrinche ◽  
Denyse Ozanne ◽  
Jean-Pierre Lebreton ◽  
Marc Fontaine ◽  
...  
Keyword(s):  
Factor H ◽  
Complement Factor H ◽  
In Vivo Studies ◽  
Complement Factor ◽  
Differential Modulation ◽  
Tnf Α
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