scholarly journals Cytotrophoblast extracellular vesicles enhance decidual cell secretion of immune modulators via TNFα

Development ◽  
2020 ◽  
Vol 147 (17) ◽  
pp. dev187013
Author(s):  
Sara K. Taylor ◽  
Sahar Houshdaran ◽  
Joshua F. Robinson ◽  
Matthew J. Gormley ◽  
Elaine Y. Kwan ◽  
...  

ABSTRACTThe placenta releases large quantities of extracellular vesicles (EVs) that likely facilitate communication between the embryo/fetus and the mother. We isolated EVs from second trimester human cytotrophoblasts (CTBs) by differential ultracentrifugation and characterized them using transmission electron microscopy, immunoblotting and mass spectrometry. The 100,000 g pellet was enriched for vesicles with a cup-like morphology typical of exosomes. They expressed markers specific to this vesicle type, CD9 and HRS, and the trophoblast proteins placental alkaline phosphatase and HLA-G. Global profiling by mass spectrometry showed that placental EVs were enriched for proteins that function in transport and viral processes. A cytokine array revealed that the CTB 100,000 g pellet contained a significant amount of tumor necrosis factor α (TNFα). CTB EVs increased decidual stromal cell (dESF) transcription and secretion of NF-κB targets, including IL8, as measured by qRT-PCR and cytokine array. A soluble form of the TNFα receptor inhibited the ability of CTB 100,000 g EVs to increase dESF secretion of IL8. Overall, the data suggest that CTB EVs enhance decidual cell release of inflammatory cytokines, which we theorize is an important component of successful pregnancy.

Author(s):  
Dmitriy S. Verkhoturov ◽  
Bruno P. Crulhas ◽  
Michael J. Eller ◽  
Yong D. Han ◽  
Stanislav V. Verkhoturov ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3770
Author(s):  
Željka Peršurić ◽  
Sandra Kraljević Pavelić

In recent years, interest has surged among researchers to determine compounds from bee products such as honey, royal jelly, propolis and bee pollen, which are beneficial to human health. Mass spectrometry techniques have shown that bee products contain a number of proven health-promoting compounds but also revealed rather high diversity in the chemical composition of bee products depending on several factors, such as for example botanical sources and geographical origin. In the present paper, we present recent scientific advances in the field of major bioactive compounds from bee products and corresponding regenerative properties. We also discuss extracellular vesicles from bee products as a potential novel bioactive nutraceutical component. Extracellular vesicles are cell-derived membranous structures that show promising potential in various therapeutic areas. It has been extensively reported that the use of vesicles, which are naturally formed in plant and animal cells, as delivery agents have many advantages. Whether the use of extracellular vesicles from bee products represents a new solution for wound healing remains still to be elucidated. However, promising results in specific applications of the bee products in wound healing and tissue regenerative properties of extracellular vesicles provide a good rationale to further explore this idea.


2021 ◽  
Vol 224 (2) ◽  
pp. S75-S76
Author(s):  
Megan Shepherd ◽  
Enkhtuya Radnaa ◽  
Rheanna Urrabaz-Garza ◽  
Talar Kechichian ◽  
Ourlad Alzeus G. Tantengco ◽  
...  

2021 ◽  
Vol 233 ◽  
pp. 104067
Author(s):  
Petr Prikryl ◽  
Veronika Satrapova ◽  
Jana Frydlova ◽  
Zdenka Hruskova ◽  
Tomas Zima ◽  
...  

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Christien M. Beez ◽  
Marion Haag ◽  
Oliver Klein ◽  
Sophie Van Linthout ◽  
Michael Sittinger ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6145
Author(s):  
Svetlana E. Novikova ◽  
Natalia A. Soloveva ◽  
Tatiana E. Farafonova ◽  
Olga V. Tikhonova ◽  
Pao-Chi Liao ◽  
...  

The proteins of extracellular vesicles (EVs) that originate from tumors reflect the producer cells’ proteomes and can be detected in biological fluids. Thus, EVs provide proteomic signatures that are of great interest for screening and predictive cancer diagnostics. By applying targeted mass spectrometry with stable isotope-labeled peptide standards, we assessed the levels of 28 EV-associated proteins, including the conventional exosome markers CD9, CD63, CD81, CD82, and HSPA8, in vesicles derived from the lung cancer cell lines NCI-H23 and A549. Furthermore, we evaluated the detectability of these proteins and their abundance in plasma samples from 34 lung cancer patients and 23 healthy volunteers. The abundance of TLN1, TUBA4A, HSPA8, ITGB3, TSG101, and PACSIN2 in the plasma of lung cancer patients was measured using targeted mass spectrometry and compared to that in plasma from healthy volunteers. The most diagnostically potent markers were TLN1 (AUC, 0.95), TUBA4A (AUC, 0.91), and HSPA8 (AUC, 0.88). The obtained EV proteomic signature allowed us to distinguish between the lung adenocarcinoma and squamous cell carcinoma histological types. The proteomic cargo of the extracellular vesicles represents a promising source of potential biomarkers.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Yang ◽  
Jin'en Wu ◽  
Yong Fu ◽  
Lujun Yan ◽  
Yating Li ◽  
...  

Echinococcosis, mainly caused by Echinococcus granulosus, is one of the 17 neglected tropical diseases. Extracellular vesicles (EVs) play an essential role in the host–parasite interplay. However, the EVs in the hydatid fluid (HF) of E. granulosus are not fully characterized. Herein, three different types of HF EVs, designated as 2 K, 10 K, and 110 K EVs based on the centrifugal force used, were morphologically identified. A total of 97, 80, and 581 proteins were identified in 2 K, 10 K, and 110 K EVs, respectively, 39 of which were commonly shared. Moreover, 11, 8, and 25 miRNAs were detected, respectively, and all of the 7 selected miRNAs were validated by qPCR to be significantly lower abundant than that in protoscoleces. It was further deemed that 110 K EVs were internalized by sheep peripheral blood mononuclear cells (PBMCs) in a time-dependent manner and thus induced interleukin (IL)-10, tumor necrosis factor-α (TNF-α), and IRF5 were significantly upregulated and IL-1β, IL-17, and CD14 were significantly downregulated (p < 0.05). These data demonstrate the physical discrepancy of three HF EVs and an immunomodulatory effect of 110 K EVs on sheep PMBCs, suggesting a role in immune responses during E. granulosus infection.


2006 ◽  
Vol 393 (3) ◽  
pp. 609-618 ◽  
Author(s):  
Alexander Stoeck ◽  
Sascha Keller ◽  
Svenja Riedle ◽  
Michael P. Sanderson ◽  
Steffen Runz ◽  
...  

Ectodomain shedding is a proteolytic mechanism by which transmembrane molecules are converted into a soluble form. Cleavage is mediated by metalloproteases and proceeds in a constitutive or inducible fashion. Although believed to be a cell-surface event, there is increasing evidence that cleavage can take place in intracellular compartments. However, it is unknown how cleaved soluble molecules get access to the extracellular space. By analysing L1 (CD171) and CD44 in ovarian carcinoma cells, we show in the present paper that the cleavage induced by ionomycin, APMA (4-aminophenylmercuric acetate) or MCD (methyl-β-cyclodextrin) is initiated in an endosomal compartment that is subsequently released in the form of exosomes. Calcium influx augmented the release of exosomes containing functionally active forms of ADAM10 (a disintegrin and metalloprotease 10) and ADAM17 [TACE (tumour necrosis factor α-converting enzyme)] as well as CD44 and L1 cytoplasmic cleavage fragments. Cleavage could also proceed in released exosomes, but only depletion of ADAM10 by small interfering RNA blocked cleavage under constitutive and induced conditions. In contrast, cleavage of L1 in response to PMA occurred at the cell surface and was mediated by ADAM17. We conclude that different ADAMs are involved in distinct cellular compartments and that ADAM10 is responsible for shedding in vesicles. Our findings open up the possibility that exosomes serve as a platform for ectodomain shedding and as a vehicle for the cellular export of soluble molecules.


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