scholarly journals Conceptus-induced, interferon tau dependent gene expression in bovine endometrial epithelial and stromal cells†

2020 ◽  
Author(s):  
Heather L Chaney ◽  
Lindsay F Grose ◽  
Gilles Charpigny ◽  
Susanta K Behura ◽  
I Martin Sheldon ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Cell Types ◽  
Stromal Fibroblast ◽  
Type I ◽  
Interferon Tau ◽  
Transcriptomic Response ◽  
Ghrelin Receptor ◽  
Biologically Relevant ◽  
Slc Transporters ◽  
Early Developmental

Abstract Bovine endometrium consists of epithelial and stromal cells that respond to conceptus interferon tau (IFNT), the maternal recognition of pregnancy (MRP) signal, by increasing expression of IFN-stimulated genes (ISGs). Endometrial epithelial and stromal cell specific ISGs are largely unknown but hypothesized to have essential functions during pregnancy establishment. Bovine endometrial epithelial cells were cultured in inserts above stromal fibroblast (SF) cells for 6 h in medium alone or with IFNT. The epithelial and SF transcriptomic response was analyzed separately using RNA sequencing and compared to a list of 369 DEGs recently identified in intact bovine endometrium in response to elongating bovine conceptuses and IFNT. Bovine endometrial epithelial and SF shared 223 and 70 DEGs in common with the list of 369 endometrial DEGs. Well known ISGs identified in the epithelial and SF were ISG15, MX1, MX2, and OAS2. DEGs identified in the epithelial but not SF included a number of IRF molecules (IRF1, IRF2, IRF3 and IRF8), mitochondria SLC transporters (SLC25A19, SLC25A28 and SLC25A30), and a ghrelin receptor (GHSR). Expression of ZC3HAV1, an anti-retroviral gene, increased specifically within the SF. Gene ontology analysis identified the type I IFN signaling pathway and activation of nuclear factor kappa B transcription factors as biological processes associated with the epithelial cell DEGs. This study has identified biologically relevant IFNT stimulated genes within specific endometrial cell types. The findings provide critical information regarding the effects of conceptus IFNT on specific endometrial compartments during early developmental processes in cattle.

scholarly journals Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through STING

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sytse J Piersma ◽  
Jennifer Poursine-Laurent ◽  
Liping Yang ◽  
Glen N Barber ◽  
Bijal A Parikh ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Plasmacytoid Dendritic Cell ◽  
Cell Types ◽  
Murine Cytomegalovirus ◽  
Type I ◽  
Viral Control ◽  
Independent Manner ◽  
Dna Viruses ◽  
Distinct Cell ◽  
Tissue Tropisms

Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while we confirmed plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.

scholarly journals Differential Production of Cartilage ECM in 3D Agarose Constructs by Equine Articular Cartilage Progenitor Cells and Mesenchymal Stromal Cells

2020 ◽  
Vol 21 (19) ◽  
pp. 7071
Author(s):  
Stefanie Schmidt ◽  
Florencia Abinzano ◽  
Anneloes Mensinga ◽  
Jörg Teßmar ◽  
Jürgen Groll ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Progenitor Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Cell Types ◽  
Type I ◽  
Cartilage Engineering ◽  
Hypoxic Conditions

Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and MSCs when cultured in hydrogels. Therefore, in this study, we compared chondrogenic differentiation of equine ACPCs and MSCs in agarose constructs as monocultures and as zonally layered co-cultures under both normoxic and hypoxic conditions. ACPCs and MSCs exhibited distinctly differential production of the cartilaginous extracellular matrix (ECM). For ACPC constructs, markedly higher glycosaminoglycan (GAG) contents were determined by histological and quantitative biochemical evaluation, both in normoxia and hypoxia. Differential GAG production was also reflected in layered co-culture constructs. For both cell types, similar staining for type II collagen was detected. However, distinctly weaker staining for undesired type I collagen was observed in the ACPC constructs. For ACPCs, only very low alkaline phosphatase (ALP) activity, a marker of terminal differentiation, was determined, in stark contrast to what was found for MSCs. This study underscores the potential of ACPCs as a promising cell source for cartilage engineering.

scholarly journals Influence of Tumor Microenvironment and Fibroblast Population Plasticity on Melanoma Growth, Therapy Resistance and Immunoescape

2021 ◽  
Vol 22 (10) ◽  
pp. 5283
Author(s):  
Veronica Romano ◽  
Immacolata Belviso ◽  
Alessandro Venuta ◽  
Maria Rosaria Ruocco ◽  
Stefania Masone ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Normal Skin ◽  
Cell Types ◽  
Therapy Resistance ◽  
Dermal Fibroblasts ◽  
Stromal Fibroblast ◽  
Cellular Interactions ◽  
Cellular Modifications

Cutaneous melanoma (CM) tissue represents a network constituted by cancer cells and tumor microenvironment (TME). A key feature of CM is the high structural and cellular plasticity of TME, allowing its evolution with disease and adaptation to cancer cell and environmental alterations. In particular, during melanoma development and progression each component of TME by interacting with each other and with cancer cells is subjected to dramatic structural and cellular modifications. These alterations affect extracellular matrix (ECM) remodelling, phenotypic profile of stromal cells, cancer growth and therapeutic response. The stromal fibroblast populations of the TME include normal fibroblasts and melanoma-associated fibroblasts (MAFs) that are highly abundant and flexible cell types interacting with melanoma and stromal cells and differently influencing CM outcomes. The shift from the normal microenvironment to TME and from normal fibroblasts to MAFs deeply sustains CM growth. Hence, in this article we review the features of the normal microenvironment and TME and describe the phenotypic plasticity of normal dermal fibroblasts and MAFs, highlighting their roles in normal skin homeostasis and TME regulation. Moreover, we discuss the influence of MAFs and their secretory profiles on TME remodelling, melanoma progression, targeted therapy resistance and immunosurveillance, highlighting the cellular interactions, the signalling pathways and molecules involved in these processes.

scholarly journals Type-I interferons are potent inhibitors of interleukin-8 production in hematopoietic and bone marrow stromal cells

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2371-2378 ◽  
Author(s):  
MJ Aman ◽  
G Rudolf ◽  
J Goldschmitt ◽  
WE Aulitzky ◽  
C Lam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Line ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
De Novo ◽  
Constitutive Expression ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Type I

Abstract nterleukin-8 (IL-8) is produced by many cell types upon stimulation with bacterial products or inflammation-associated cytokines such as tumor necrosis factor-alpha and IL-1. Interferons (IFNs) represent another group of cytokines that are induced by similar stimuli in inflammatory reactions. We show now that type-I IFNs are potent inhibitors of IL-8 expression in vitro and in vivo. A significant reduction of both secretion of IL-8 protein and accumulation of IL-8 mRNA in vitro was observed in several cell types comprising peripheral blood mononuclear cells (PBMNC) from healthy donors and from patients with chronic myelogenous leukemia (CML), the myelomonocytic cell line THP-1, and bone marrow (BM) stromal cells as a representative model for BM microenvironment. By contrast, in lipopolysaccharide-stimulated polymorphonuclear phagocytes IFN failed to suppress IL-8 expression. In untreated patients with CML, a constitutive expression of IL-8 mRNA was detected in freshly isolated PBMNC that was markedly reduced 5 hours after therapeutic application of IFN-alpha. The mechanism of IL-8 downregulation was studied more in detail in the THP-1 cell line. The experiments showed that de novo protein synthesis was not required for the inhibitory effect. RNA decay analysis and nuclear run-on assays suggest that in THP-1 cell line the inhibition of IL-8 expression is predominantly regulated at the posttranscriptional level.

Natural and recombinant bovine interferon tau regulate basal and oxytocin-induced secretion of prostaglandins F2 alpha and E2 by epithelial cells and stromal cells in the endometrium

1994 ◽  
Vol 6 (2) ◽  
pp. 193 ◽  
Author(s):  
G Danet-Desnoyers ◽  
C Wetzels ◽  
WW Thatcher
Keyword(s):  
Epithelial Cells ◽  
Effective Dose ◽  
Stromal Cells ◽  
Culture Medium ◽  
Cell Types ◽  
Endometrial Tissue ◽  
Endometrial Cell ◽  
Basal Secretion ◽  
Interferon Tau ◽  
Minimal Effective Dose

The effects of bovine interferon tau (IFN tau) and oxytocin on secretion of the prostaglandins PGF2 alpha and PGE2 by epithelial and stromal cells in the endometrium were assessed in two experiments. Endometrial tissues were collected from cyclic cows at Day 15 after oestrus for subsequent isolation of epithelial cells (4 cows) and stromal cells (4 cows). In both experiments, confluent cells were treated with 0, 2, 10 or 50 ng mL-1 natural bovine IFN tau (nbIFN tau) or 0, 0.4, 2, 10, 50 and 250 ng mL-1 recombinant bIFN tau (rbIFN tau). Culture medium was sampled at 24 h. Oxytocin (2.0 x 10(-7) M) or placebo was then added to wells and the medium was sampled 30 and 90 min later. Epithelial cells secreted more PGF2 alpha than stromal cells whereas stromal cells predominantly secreted PGE2. Oxytocin stimulated secretion of PGF2 alpha and PGE2 (P < 0.01) from epithelial cells, but both basal secretion and oxytocin-induced secretion of PGF2 alpha and PGE2 decreased with increasing dose of either nbIFN tau or rbIFN tau (P < 0.01). At comparable doses, rbIFN tau inhibited PGF2 alpha and PGE2 secretion more strongly than did nbIFN tau (either in the absence or the presence of oxytocin). The minimal effective dose of rbIFN tau was 0.4 ng mL-1 and 50% inhibition was obtained with 1 ng mL-1 (0.043 nM). Neither nbIFN tau nor rbIFN tau nor oxytocin altered PGF2 alpha or PGE2 secretion by stromal cells. The results indicate differential prostaglandin responses by the two major endometrial cell types (epithelium and stroma) to regulatory agents such as bIFN tau and oxytocin in cattle. Suppression of prostaglandin secretion by bIFN tau in epithelial cells of endometrial tissue is supportive of an antiluteolytic effect of bIFN tau.

scholarly journals Virus infection is controlled by cell type-specific sensing of murine cytomegalovirus through MyD88 and STING

2020 ◽  
Author(s):  
Sytse J. Piersma ◽  
Jennifer Poursine-Laurent ◽  
Liping Yang ◽  
Glen N. Barber ◽  
Bijal A. Parikh ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Plasmacytoid Dendritic Cell ◽  
Cell Types ◽  
Murine Cytomegalovirus ◽  
Type I ◽  
Viral Control ◽  
Independent Manner ◽  
Dna Viruses ◽  
Distinct Cell ◽  
Tissue Tropisms

AbstractRecognition of DNA viruses, such as cytomegaloviruses (CMVs), through patternrecognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we investigated anti-viral effects of MyD88 and STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer (NK) cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.

scholarly journals Type-I interferons are potent inhibitors of interleukin-8 production in hematopoietic and bone marrow stromal cells

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2371-2378 ◽  
Author(s):  
MJ Aman ◽  
G Rudolf ◽  
J Goldschmitt ◽  
WE Aulitzky ◽  
C Lam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Line ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
De Novo ◽  
Constitutive Expression ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Type I

nterleukin-8 (IL-8) is produced by many cell types upon stimulation with bacterial products or inflammation-associated cytokines such as tumor necrosis factor-alpha and IL-1. Interferons (IFNs) represent another group of cytokines that are induced by similar stimuli in inflammatory reactions. We show now that type-I IFNs are potent inhibitors of IL-8 expression in vitro and in vivo. A significant reduction of both secretion of IL-8 protein and accumulation of IL-8 mRNA in vitro was observed in several cell types comprising peripheral blood mononuclear cells (PBMNC) from healthy donors and from patients with chronic myelogenous leukemia (CML), the myelomonocytic cell line THP-1, and bone marrow (BM) stromal cells as a representative model for BM microenvironment. By contrast, in lipopolysaccharide-stimulated polymorphonuclear phagocytes IFN failed to suppress IL-8 expression. In untreated patients with CML, a constitutive expression of IL-8 mRNA was detected in freshly isolated PBMNC that was markedly reduced 5 hours after therapeutic application of IFN-alpha. The mechanism of IL-8 downregulation was studied more in detail in the THP-1 cell line. The experiments showed that de novo protein synthesis was not required for the inhibitory effect. RNA decay analysis and nuclear run-on assays suggest that in THP-1 cell line the inhibition of IL-8 expression is predominantly regulated at the posttranscriptional level.

scholarly journals Charged Residues Flanking the Transmembrane Domain of Two Related Toxin–Antitoxin System Toxins Affect Host Response

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 329
Author(s):  
Andrew Holmes ◽  
Jessie Sadlon ◽  
Keith Weaver
Keyword(s):  
Amino Acid ◽  
Enterococcus Faecalis ◽  
Host Response ◽  
Cytoplasmic Membrane ◽  
Transmembrane Domain ◽  
The Other ◽  
Type I ◽  
Transcriptomic Response ◽  
Specific Amino Acid ◽  
Transporter Protein

A majority of toxins produced by type I toxin–antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

scholarly journals The Selective Histone Deacetylase Inhibitor MI192 Enhances the Osteogenic Differentiation Efficacy of Human Dental Pulp Stromal Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5224
Author(s):  
Kenny Man ◽  
Liam Lawlor ◽  
Lin-Hua Jiang ◽  
Xuebin B. Yang
Keyword(s):  
Alkaline Phosphatase ◽  
Osteogenic Differentiation ◽  
Stromal Cells ◽  
Dental Pulp ◽  
Selective Inhibitor ◽  
Epigenetic Reprogramming ◽  
Type I ◽  
Human Dental Pulp ◽  
Pre Treatment ◽  
Dose Dependent

The use of human dental pulp stromal cells (hDPSCs) has gained increasing attention as an alternative stem cell source for bone tissue engineering. The modification of the cells’ epigenetics has been found to play an important role in regulating differentiation, with the inhibition of histone deacetylases 3 (HDAC3) being linked to increased osteogenic differentiation. This study aimed to induce epigenetic reprogramming using the HDAC2 and 3 selective inhibitor, MI192 to promote hDPSCs osteogenic capacity for bone regeneration. MI192 treatment caused a time–dose-dependent change in hDPSC morphology and reduction in viability. Additionally, MI192 successfully augmented hDPSC epigenetic functionality, which resulted in increased histone acetylation and cell cycle arrest at the G2/M phase. MI192 pre-treatment exhibited a dose-dependent effect on hDPSCs alkaline phosphatase activity. Quantitative PCR and In-Cell Western further demonstrated that MI192 pre-treatment significantly upregulated hDPSCs osteoblast-related gene and protein expression (alkaline phosphatase, bone morphogenic protein 2, type I collagen and osteocalcin) during osteogenic differentiation. Importantly, MI192 pre-treatment significantly increased hDPSCs extracellular matrix collagen production and mineralisation. As such, for the first time, our findings show that epigenetic reprogramming with the HDAC2 and 3 selective inhibitor MI192 accelerates the osteogenic differentiation of hDPSCs, demonstrating the considerable utility of this MSCs engineering approach for bone augmentation strategies.

scholarly journals Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies

2021 ◽  
Vol 22 (14) ◽  
pp. 7536
Author(s):  
Inez Wens ◽  
Ibo Janssens ◽  
Judith Derdelinckx ◽  
Megha Meena ◽  
Barbara Willekens ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Treatment Options ◽  
Cell Types ◽  
Peripheral Blood Mononuclear ◽  
Tailored Treatment ◽  
Key Issues ◽  
The Central Nervous System

Currently, there is still no cure for multiple sclerosis (MS), which is an autoimmune and neurodegenerative disease of the central nervous system. Treatment options predominantly consist of drugs that affect adaptive immunity and lead to a reduction of the inflammatory disease activity. A broad range of possible cell-based therapeutic options are being explored in the treatment of autoimmune diseases, including MS. This review aims to provide an overview of recent and future advances in the development of cell-based treatment options for the induction of tolerance in MS. Here, we will focus on haematopoietic stem cells, mesenchymal stromal cells, regulatory T cells and dendritic cells. We will also focus on less familiar cell types that are used in cell therapy, including B cells, natural killer cells and peripheral blood mononuclear cells. We will address key issues regarding the depicted therapies and highlight the major challenges that lie ahead to successfully reverse autoimmune diseases, such as MS, while minimising the side effects. Although cell-based therapies are well known and used in the treatment of several cancers, cell-based treatment options hold promise for the future treatment of autoimmune diseases in general, and MS in particular.

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