scholarly journals Uvaol Prevents Group B Streptococcus-Induced Trophoblast Cells Inflammation and Possible Endothelial Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Lucia Mendes Silva ◽  
Elaine Cristina Oliveira Silva ◽  
Rayane Martins Botelho ◽  
Liliane Patricia Gonçalves Tenorio ◽  
Aldilane Lays Xavier Marques ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Line ◽  
Group B Streptococcus ◽  
Trophoblast Invasion ◽  
Trophoblast Cells ◽  
Chorionic Villi ◽  
Group B ◽  
Angiopoietin 2 ◽  
And Function

Group B Streptococcus (GBS) infection during pregnancy is involved in maternal sepsis, chorioamnionitis, prematurity, fetal infection, neonatal sepsis, and neurodevelopmental alterations. The GBS-induced chorioamnionitis leads to a plethora of immune and trophoblast cells alterations that could influence endothelial cells to respond differently to angiogenic mediators and alter placental vascular structure and function in pregnant women. In this context, preventive measures are needed to reduce such dysfunctions. As such, we evaluated the effects of a non-lethal exposure to inactivated GBS on trophoblast cells and chorionic villi explants, and if the treatment with uvaol would mitigate these effects. The concentration of 106 CFU of GBS was chosen since it was unable to reduce the HTR-8/SVneo cell line nor term chorionic villi explant viability. Raman spectroscopy of trophoblast cells showed significant alterations in their biochemical signature, mostly reverted by uvaol. GBS exposure increased HTR-8/SVneo cells IL-1β and IFN-γ production, phagocytosis, oxidative stress, and decreased trophoblast cell migration. The Ea.hy926 endothelial cell line produced angiopoietin-2, CXCL-8, EGF, FGF-b, IL-6, PlGF, sPECAM-1, and VEGF in culture. When co-cultured in invasion assay with HTR-8/SVneo trophoblast cells, the co-culture had increased production of angiopoietin-2, CXCL-8, FGF-b, and VEGF, while reduced sPECAM-1 and IL-6. GBS exposure led to increased CXCL-8 and IL-6 production, both prevented by uvaol. Chorionic villi explants followed the same patterns of production when exposed to GBS and response to uvaol treatment as well. These findings demonstrate that, even a non-lethal concentration of GBS causes placental inflammation and oxidative stress, reduces trophoblast invasion of endothelial cells, and increases CXCL-8 and IL-6, key factors that participate in vascular dysregulation observed in several diseases. Furthermore, uvaol treatment prevented most of the GBS-provoked changes. Hence, uvaol could prevent the harmful effects of GBS infection for both the mother and the fetus.

scholarly journals Infection of Human Coronary Artery Endothelial Cells by Group B Streptococcus Contributes to Dysregulation of Apoptosis, Hemostasis, and Innate Immune Responses

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Claudia Beyrich ◽  
Jürgen Löffler ◽  
Anna Kobsar ◽  
Christian P. Speer ◽  
Susanne Kneitz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Group B Streptococcus ◽  
Gene Array ◽  
Neonatal Morbidity ◽  
Innate Immune ◽  
Human Coronary Artery ◽  
Chemotactic Protein ◽  
Early Onset Sepsis ◽  
Group B

Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocyte chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis.

scholarly journals Development and Application of a High-Content Virion Display Human GPCR Array

2018 ◽  
Author(s):  
Guan-Da Syu ◽  
Shih-Chin Wang ◽  
Guangzhong Ma ◽  
Shuang Liu ◽  
Donna Pearce ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
High Throughput ◽  
Group B Streptococcus ◽  
Biochemical Properties ◽  
Neonatal Meningitis ◽  
Native Conformation ◽  
Herpes Simplex Virus 1 ◽  
Group B ◽  
Simplex Virus ◽  
And Function

ABSTRACTG protein-coupled receptors (GPCRs) comprise the largest membrane protein family in humans and can respond to a wide variety of ligands and stimuli. Like other multi-pass membrane proteins, the biochemical properties of GPCRs are notoriously difficult to study because they must be embedded in lipid bilayers to maintain their native conformation and function. To enable an unbiased, high-throughput platform to profile biochemical activities of GPCRs in native conformation, we individually displayed 315 human non-odorant GPCRs (>85% coverage) in the envelope of human herpes simplex virus-1 and immobilized on glass to form a high-content Virion Display (VirD) array. Using this array, we found that 50% of the tested commercial anti-GPCR antibodies (mAbs) is ultra-specific, and that the vast majority of those VirD-GPCRs, which failed to be recognized by the commercial mAbs, could bind to their canonical ligands, indicating that they were folded correctly. Next, we used the VirD-GPCR arrays to examine binding specificity of two known peptide ligands and recovered expected interactions, as well as new off-target interactions, three of which were confirmed with real-time kinetics measurements. Finally, we explored the possibility of discovering novel pathogen targets by probing VirD-GPCR arrays with live group B Streptococcus (GBS), a common Gram-positive bacterium causing neonatal meningitis. Using cell invasion assays and a mouse model of hematogenous meningitis, we showed that inhibition of one of the five newly identified GPCRs, CysLTR1, greatly reduced GBS penetration in brain-derived endothelial cells and in mouse brains. Therefore, our work demonstrated that the VirD-GPCR array holds great potential for high-throughput, unbiased screening for small molecule drugs, affinity reagents, and deorphanization.

Spectrum of Changes Seen With Placental Intravascular Organisms

2018 ◽  
Vol 22 (3) ◽  
pp. 229-235 ◽  
Author(s):  
Pawel T Schubert ◽  
Deidre Mason ◽  
Roosacelis Martines ◽  
Marlene Deleon-Carnes ◽  
Sherif R Zaki ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Bacterial Infections ◽  
Fetal Death ◽  
Group B Streptococcus ◽  
Congenital Infection ◽  
Neonatal Morbidity ◽  
Chorionic Villi ◽  
Congenital Infections ◽  
Ascending Infection ◽  
Group B

Fetal bacterial infections are a common cause of fetal/neonatal morbidity and mortality. The pathologic correlates of congenital bacterial infection include acute chorioamnionitis, acute villitis, and acute intervillositis. The strength of the association of congenital bacterial infection differs among these pathologies. Acute chorioamnionitis results usually from an ascending infection, and damage to the fetus is thought to be cytokine driven rather than damage secondary to bacteremia. Acute villitis is strongly associated with fetal sepsis due to congenital infections. A much less common variant on acute villitis pattern has been described with additional presence of bacteria in the fetal capillaries of the chorionic villi. We describe the spectrum of bacteria that would induce this unique pattern. The histological archives were searched from 2 institutions for cases with intravascular bacteria present in the villous capillaries of the placenta. Thirteen cases were identified, of which 11 cases had acute chorioamnionitis and all cases showed an acute villitis. Eight cases had Escherichia coli identified and 3 cases had Group B Streptococcus. All cases were associated with fetal death. In 9 cases, the mother showed signs of a significant infection including 1 maternal death. We conclude that finding intravascular bacteria is a serious complication of congenital infection with serious fetal and maternal sequela.

scholarly journals Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Bin He ◽  
Qi Yue Li ◽  
Yuan Yuan Wu ◽  
Jing Ling Ruan ◽  
Xiao Ming Teng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cyclosporin A ◽  
Signaling Pathways ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Trophoblast Invasion ◽  
Trophoblast Cells ◽  
Induced Apoptosis

Abstract Background Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis. Methods JEG-3 cells were cocultured with H2O2 and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting. Results CsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the H2O2-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with H2O2. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the H2O2-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis. Conclusions These results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways.

scholarly journals Regulation and Function of Pilus Island 1 in Group B Streptococcus

2012 ◽  
Vol 194 (10) ◽  
pp. 2479-2490 ◽  
Author(s):  
S. Jiang ◽  
S. E. Park ◽  
P. Yadav ◽  
L. C. Paoletti ◽  
M. R. Wessels
Keyword(s):  
Group B Streptococcus ◽  
Group B ◽  
And Function

In vitro evaluation of uvaol treatment in term chorionic villi explants incubated with group B streptococcus

Placenta ◽  
2021 ◽  
Vol 112 ◽  
pp. e42
Author(s):  
Ashelley Sousa ◽  
Ingredy Rodrigues ◽  
Larissa Almeida ◽  
Monique Nova ◽  
Maria Santos ◽  
...  
Keyword(s):  
Group B Streptococcus ◽  
Chorionic Villi ◽  
In Vitro Evaluation ◽  
Group B

scholarly journals Hemangiosarcoma cells induce M2 polarization and PD-L1 expression in macrophages

2021 ◽  
Author(s):  
Kevin Christian M. Gulay ◽  
Keisuke Aoshima ◽  
Naoya Maekawa ◽  
Satoru Konnai ◽  
Atsushi Kobayashi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Cell Line ◽  
Expression Patterns ◽  
Major Constituent ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Syngeneic Mouse Model ◽  
And Function

Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells. Tumor-associated macrophages are one of the major components of tumor microenvironment and crucial for cancer development. The presence and function of macrophages in HSA have not been studied because there is no syngeneic model for HSA. In this study, we evaluated two mouse HSA cell lines and one immortalized mouse endothelial cells for their usefulness as syngeneic models for canine HSA. Our results show that the ISOS-1 cell line develops tumors with similar morphology to canine HSA. ISOS-1 cells highly express KDM2B and have similar KDM2B target expression patterns with canine HSA. Moreover, we determine that in both ISOS-1 and canine HSA tumors, macrophages are present as a major constituent of the tumor microenvironment. These macrophages are positive for CD204, an M2 macrophage marker, and express PD-L1. ISOS-1-conditioned medium can induce M2 polarization and PD-L1 expression in RAW264.7 mouse macrophage cell line. These results show that ISOS-1 can be used as a syngenic model for canine HSA and suggest that macrophages play an important role in immune evasion in HSA. Using the syngeneic mouse model for canine HSA, we can further study the role of immune cells in the pathology of HSA.

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