scholarly journals Bovine endometrial cells do not mount an inflammatory response to Leptospira

2021 ◽  
Author(s):  
Paula C. C. Molinari ◽  
Jarlath E Nally ◽  
John J Bromfield
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Outer Membrane ◽  
Reproductive Tract ◽  
The United States ◽  
Reproductive Failure ◽  
Female Reproductive Tract ◽  
Human Monocytes ◽  
Endometrial Cells ◽  
Endometrial Epithelial Cells

Leptospirosis causes abortion, premature birth, and stillbirth in cattle, but the mechanisms remain unclear. Infected cattle shed Leptospira intermittently and present a range of clinical symptoms, making diagnosis difficult. The primary route of Leptospira transmission in any animal is colonization of the renal tubule and excretion by urine, however Leptospira can also colonize the female reproductive tract of cows and can be transmitted by semen. Vaccination against Leptospira in the United States is routine in cattle, but immunity is not guaranteed. The cell wall of Leptospira contains Toll-like receptor agonists including peptidoglycan and lipopolysaccharide. The capacity of Leptospira to initiate an innate inflammatory response from uterine endometrial cells is unknown but may be a cause of reproductive failure. Using cell culture, we tested the capacity of bovine endometrial epithelial cells or human monocytes to elicit an inflammatory response to Leptospira borgpetersenii serovar Hardjo strain TC273. Cells were exposed to either heat-killed Leptospira, Leptospira outer membrane, Escherichia coli lipopolysaccharide, Pam3CSK4 or medium alone for 2 to 24 hours. Exposure of bovine endometrial epithelial cells or human monocytes to heat-killed Leptospira or Leptospira outer membrane did not induce the expression of IL1A, IL1B, IL6 or CXCL8, while exposure to E. coli lipopolysaccharide or Pam3CSK4 increased expression of IL1A, IL1B, IL6 and CXCL8 compared to control cells. This data suggests that Leptospira does not trigger a classical inflammatory response in endometrial cells. Understanding the interaction between Leptospira and the female reproductive tract is important in determining the mechanisms of Leptospirosis associated reproductive failure.

scholarly journals Lipocalin 2 induces the epithelial–mesenchymal transition in stressed endometrial epithelial cells: possible correlation with endometriosis development in a mouse model

Reproduction ◽  
2014 ◽  
Vol 147 (2) ◽  
pp. 179-187 ◽  
Author(s):  
Chi-Jr Liao ◽  
Pei-Tzu Li ◽  
Ying-Chu Lee ◽  
Sheng-Hsiang Li ◽  
Sin Tak Chu
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Lipocalin 2 ◽  
Mesenchymal Transition ◽  
Endometrial Cells ◽  
Cellular Microenvironments ◽  
And Migration ◽  
Endometrial Epithelial Cells

Lipocalin 2 (LCN2) is an induced stressor that promotes the epithelial–mesenchymal transition (EMT). We previously demonstrated that the development of endometriosis in mice correlates with the secretion of LCN2 in the uterus. Here, we sought to clarify the relationship between LCN2 and EMT in endometrial epithelial cells and to determine whether LCN2 plays a role in endometriosis. Antibodies that functionally inhibit LCN2 slowed the growth of ectopic endometrial tissue in a mouse model of endometriosis, suggesting that LCN2 promotes the formation of endometriotic lesions. Using nutrient deprivation as a stressor, LCN2 expression was induced in cultured primary endometrial epithelial cells. As LCN2 levels increased, the cells transitioned from a round to a spindle-like morphology and dispersed. Immunochemical analyses revealed decreased levels of cytokeratin and increased levels of fibronectin in these endometrial cells, adhesive changes that correlate with induction of cell migration and invasion.Lcn2knockdown also indicated that LCN2 promotes EMT and migration of endometrial epithelial cells. Our results suggest that stressful cellular microenvironments cause uterine tissues to secrete LCN2 and that this results in EMT of endometrial epithelial cells, which may correlate with the development of ectopic endometriosis. These findings shed light on the role of LCN2 in the pathology of endometrial disorders.

scholarly journals Inflammatory Response Elicited by Ureaplasma parvum colonization in human cervical epithelial, stromal, and immune cells

Reproduction ◽  
2021 ◽  
Author(s):  
Ourlad Alzeus Gaddi Tantengco ◽  
Talar Kechichian ◽  
Kathleen L Vincent ◽  
Richard B Pyles ◽  
Paul Mark B Medina ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Stromal Cells ◽  
Female Reproductive Tract ◽  
Ureaplasma Parvum ◽  
Cervical Epithelial Cells ◽  
Anti Inflammatory ◽  
The Impact

Ureaplasma parvum is a commensal bacterium in the female reproductive tract but has been associated with pregnancy complications such as preterm prelabor rupture of membranes and preterm birth (PTB). However, the pathologic effects of U. parvum in the cervix, that prevents ascending infections during pregnancy, are still poorly understood. To determine the impact of U. parvum on the cervix, ectocervical (ecto) and endocervical (endo) epithelial and stromal cells were incubated with U. parvum. Macrophages were also tested as a proxy for cervical macrophages to determine the antigenicity of U. parvum. The effects of U. parvum, including influence on cell cycle and cell death, antimicrobial peptide production, epithelial-to-mesenchymal transition (EMT), and inflammatory cytokine levels, were assessed. U. parvum colonized cervical epithelial and stromal cells 4 hours post-infection. Like uninfected control, U. parvum neither inhibited cell cycle progression and nor caused cell death in cervical epithelial and stromal cells. U. parvum increased the production of the antimicrobial peptides (AMPs) cathelicidin and human β-defensin 3 and exhibited weak signs of EMT evidenced by decreased cytokeratin 18 and increased vimentin expression in cervical epithelial cells. U. parvum induced a pro-inflammatory environment (cytokines) and increased MMP-9 in cervical epithelial cells but promoted pro- and anti-inflammatory responses in cervical stromal cells and macrophages. U. parvum may colonize the cervical epithelial layer, but induction of AMPs and anti-inflammatory response may protect the cervix and may prevent ascending infections that can cause PTB. These findings suggest that U. parvum is a weak inducer of inflammation in the cervix.

421. Seminal fluid TGFβ regulates follistatin mRNA expression human Ect1 cervical epithelial cells

2008 ◽  
Vol 20 (9) ◽  
pp. 101 ◽  
Author(s):  
D. J. Sharkey ◽  
S. A. Robertson
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Mrna Expression ◽  
Seminal Plasma ◽  
Seminal Fluid ◽  
Differentially Expressed Gene ◽  
Female Reproductive Tract ◽  
High Concentration ◽  
Human Seminal Plasma ◽  
Local Inflammatory Response

Introduction of seminal fluid into the female reproductive tract following coitus stimulates a local inflammatory response. Inflammatory leukocyte recruitment is regulated by induction of cytokine and chemokine synthesis in female tract epithelial cells by seminal fluid signalling agents. Affymetrix microarray analysis in immortalised ectocervical epithelial (Ect1) cells identified the potent anti-inflammatory cytokine follistatin (FST) as the most strongly differentially expressed gene, with a ~12-fold increase in mRNA expression induced by seminal fluid. Follistatin has recently been implicated as a key cytokine in early pregnancy by studies in female follistatin null mice, which exhibit infertility as a consequence of failure to resolve the uterine post-mating inflammatory response. The aim of this study was to investigate seminal plasma regulation of follistatin in human Ect1 cervical cells, and to examine the role of the major active seminal fluid constituent, TGFβ, in controlling Ect1 cells follistatin mRNA expression. To confirm Affymetrix findings, qRT–PCR experiments were undertaken in Ect1 cells incubated with 10% pooled human seminal plasma (SP). Primers specific for the tissue bound isoform of follistatin (FST288) as well as both FST288 and the circulating 315 isoforms (FSTall) were used. Ect1 cell incubation with 10%SP elicited 3.8-fold and 4-fold increases in FST288 and FSTall respectively. Incubation of Ect1 cells with TGFβ1, TGFβ2 and TGFβ3 showed differential effects of the three isoforms, with rTGFβ2 inducing FST288 and FSTall, while rTGFβ1 and TGFβ3 exerted little effect.. These results suggest that seminal plasma induces follistatin synthesis after coitus and that TGFβ2 is at least partly responsible for this effect. Follistatin induced by seminal fluid may act to limit the course of inflammation after intercourse, and thereby prevent uncontrolled inflammatory damage. Follistatin induced in the female tissues would be augmented by follistatin delivered from the male, since human seminal plasma also contains a high concentration of this cytokine.

scholarly journals LEFTYA Activates the Epithelial Na+ Channel (ENaC) in Endometrial Cells via Serum and Glucocorticoid Inducible Kinase SGK1

2016 ◽  
Vol 39 (4) ◽  
pp. 1295-1306 ◽  
Author(s):  
Madhuri S. Salker ◽  
Zohreh Hosseinzadeh ◽  
Nour Alowayed ◽  
Ni Zeng ◽  
Anja T. Umbach ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ussing Chamber ◽  
Endometrial Adenocarcinoma ◽  
Negative Regulator ◽  
Na Channel ◽  
Uterine Receptivity ◽  
Endometrial Cells ◽  
Ishikawa Cells ◽  
Epithelial Na Channel ◽  
Endometrial Epithelial Cells

Background: Serum & glucocorticoid inducible kinase (SGK1) regulates several ion channels, including amiloride sensitive epithelial Na+ channel (ENaC). SGK1 and ENaC in the luminal endometrium epithelium, are critically involved in embryo implantation, although little is known about their regulation. The present study explored whether SGK1 and ENaC are modulated by LEFTYA, a negative regulator of uterine receptivity. Methods: Expression levels were determined by qRT-PCR and Western blotting, ENaC channel activity by whole cell patch clamp and transepithelial current by Ussing chamber experiments. Results: Treatment of Ishikawa cells, an endometrial adenocarcinoma model cell line of endometrial epithelial cells, with LEFTYA rapidly up-regulated SGK1 and ENaC transcript and protein levels. Induction of ENaC in response to LEFTYA was blunted upon co-treatment with the SGK1 inhibitor EMD638683. ENaC levels also significantly upregulated upon expression of a constitutively active, but not a kinase dead, SGK1 mutant in Ishikawa cells. LEFTYA increased amiloride sensitive Na+-currents in Ishikawa cells and amiloride sensitive transepithelial current across the murine endometrium. Furthermore, LEFTYA induced the expression of ENaC in the endometrium of wild-type but not of Sgk1-deficient mice. Conclusions: LEFTYA regulates the expression and activity of ENaC in endometrial epithelial cells via SGK1. Aberrant regulation of SGK1 and ENaC by LEFTYA could contribute to the pathogenesis of unexplained infertility.

scholarly journals Effects of Tenofovir on Cytokines and Nucleotidases in HIV-1 Target Cells and the Mucosal Tissue Environment in the Female Reproductive Tract

2014 ◽  
Vol 58 (11) ◽  
pp. 6444-6453 ◽  
Author(s):  
Nabanita Biswas ◽  
Marta Rodriguez-Garcia ◽  
Zheng Shen ◽  
Sarah G. Crist ◽  
Jack E. Bodwell ◽  
...  
Keyword(s):  
T Cells ◽  
Biological Activity ◽  
Epithelial Cells ◽  
Hiv Infection ◽  
Proinflammatory Cytokines ◽  
Reproductive Tract ◽  
Biological Activities ◽  
Female Reproductive Tract ◽  
Immune Protection ◽  
Tnf Α

ABSTRACTTenofovir (TFV) is a reverse transcriptase inhibitor used in microbicide preexposure prophylaxis trials to prevent HIV infection. Recognizing that changes in cytokine/chemokine secretion and nucleotidase biological activity can influence female reproductive tract (FRT) immune protection against HIV infection, we tested the hypothesis that TFV regulates immune protection in the FRT. Epithelial cells, fibroblasts, CD4+T cells, and CD14+cells were isolated from the endometrium (Em), endocervix (Cx), and ectocervix (Ecx) following hysterectomy. The levels of proinflammatory cytokines (macrophage inflammatory protein 3α [MIP-3α], interleukin 8 [IL-8], and tumor necrosis factor alpha [TNF-α]), the expression levels of specific nucleotidases, and nucleotidase biological activities were analyzed in the presence or absence of TFV. TFV influenced mRNA and/or protein cytokines and nucleotidases in a cell- and site-specific manner. TFV significantly enhanced IL-8 and TNF-α secretion by epithelial cells from the Em and Ecx but not from the Cx. In contrast, in response to TFV, IL-8 secretion was significantly decreased in Em and Cx fibroblasts but increased with fibroblasts from the Ecx. When incubated with CD4+T cells from the FRT, TFV increased IL-8 (Em and Ecx) and TNF-α (Cx and Ecx) secretion levels. Moreover, when incubated with Em CD14+cells, TFV significantly increased MIP-3α, IL-8, and TNF-α secretion levels relative to those of the controls. In contrast, nucleotidase biological activities were significantly decreased by TFV in epithelial (Cx) and CD4+T cells (Em) but increased in fibroblasts (Em). Our findings indicate that TFV modulates proinflammatory cytokines, nucleotidase gene expression, and nucleotidase biological activity in epithelial cells, fibroblasts, CD4+T cells, and CD14+cells at distinct sites within the FRT.

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