scholarly journals Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
S. Fromm ◽  
C. C. Cunningham ◽  
M. R. Dunne ◽  
D. J. Veale ◽  
U. Fearon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Transcriptome Analysis ◽  
Cell Function ◽  
Surface Expression ◽  
Tube Formation ◽  
Cell Surface Expression ◽  
Endothelial Cell Function

Abstract Introduction Angiogenesis is an early event in the pathogenesis of both psoriatic arthritis (PsA) and rheumatoid arthritis (RA); however, there are striking differences in blood vessel morphology and activation between the two arthropathies. The aim of this study was to assess if the PsA and RA joint microenvironments differentially regulate endothelial cell function. Methods PsA and RA primary synovial fibroblasts (SFC) were isolated from synovial biopsies, grown to confluence, and supernatants harvested and termed ‘conditioned media’ (CM). Human umbilical vein endothelial cells (HUVEC) were cultured with PsA SFC or RA SFC-CM (20%). HUVEC tube formation, migration, and PBMC adhesion were assessed by matrigel tube formation, wound repair, and PBMC adhesion assays. HUVEC cell surface expression of ICAM, VCAM, and E-Selectin was assessed by flow cytometry. Transcriptome analysis of genes promoting angiogenesis was performed by real-time PCR. Finally, a MSD multiplex angiogenic assay was performed on PsA SFC and RA SFC supernatants. Results Macroscopic synovitis and vascularity were similar in PsA and RA patients; however, significant differences in vascular morphological pattern were recorded with tortuous, elongated vessels observed in PsA compared to straight regular branching vessels observed in RA. Transcriptome analysis showed strong upregulation of the pro-angiogenic signature in HUVEC primed with PsA SFC-CM compared to RA SFC-CM and basal control. In parallel, paired PsA SFC-CM significantly induced HUVEC tube formation compared to that of RA SFC-CM. Furthermore, PsA SFC-CM induced HUVEC migration was paralleled by a significant induction in VEGFA, PFKFB3, ICAM-1, and MMP3 mRNA expression. A significant increase in PBMC adhesion and cell surface expression of VCAM-1, ICAM-1, and E-Selectin expression was also demonstrated in PsA SFC-CM-primed HUVEC compared to RA SFC-CM. Finally, VEGF, TSLP, Flt-1, and Tie-2 expression was elevated in PsA SFC-CM compared to RA SFC-CM, with no significant difference in other pro-angiogenic mediators including MIP-3, bFGF, PIGF, and MCP-1. Conclusion PsA SFC and RA SFC secreted factors differentially regulate endothelial cell function, with soluble mediators in the PsA joint microenvironment inducing a more pro-angiogenic phenotype compared to the RA.

scholarly journals Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell–mediated lysis of myeloma

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1309-1317 ◽  
Author(s):  
Jumei Shi ◽  
Guido J. Tricot ◽  
Tarun K. Garg ◽  
Priyangi A. Malaviarachchi ◽  
Susann M. Szmania ◽  
...  
Keyword(s):  
Cell Surface ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Significant Activity

AbstractHuman leukocyte antigen class I molecules expressed by tumor cells play a central role in the regulation of natural killer (NK) cell–mediated immune responses. The proteasome inhibitor bortezomib has demonstrated significant activity in multiple myeloma (MM). We hypothesized that treatment of MM with bortezomib results in the reduction of cell-surface expression of class I and thereby sensitizes MM to NK cell–mediated lysis. Here we report that bortezomib down-regulates class I in a time- and dose-dependent fashion on all MM cell lines and patient MM cells tested. Downregulation of class I can also be induced in vivo after a single dose of 1.0 mg/m2 bortezomib. Bortezomib significantly enhances the sensitivity of patient myeloma to allogeneic and autologous NK cell–mediated lysis. Further, the level of decrease in class I expression correlates with increased susceptibility to lysis by NK cells. Clinically relevant bortezomib concentrations do not affect NK-cell function. Our findings have clear therapeutic implications for MM and other NK cell–sensitive malignancies in the context of both allogeneic and autologous adoptively transferred NK cells.

Abstract 44: Restoration of Angiogenic Balance and Improved Endothelial Cell Function via Ampk Activation is Hypoxia and Ischemia Dependent in Trophoblast Cells and Pregnant Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Christopher T Banek ◽  
Ashley J Bauer ◽  
Karen M Needham ◽  
Hans C Dreyer ◽  
Jeffrey Gilbert
Keyword(s):  
Blood Pressure ◽  
Endothelial Cell ◽  
Cell Function ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Ampk Activation ◽  
Trophoblast Cells ◽  
Endothelial Cell Function ◽  
Angiogenic Balance ◽  
Stimulation Of

Previous studies indicate restoration of angiogenic balance lowers blood pressure and improves vascular endothelial cell function in several experimental models of preeclampsia. Stimulation of the adenosine monophosphate kinase (AMPK) pathway is known to increase VEGF expression. We hypothesized stimulation of AMPK with aminoimidazole carboxamide ribonucleotide (AICAR) would increase plasma VEGF, improve endothelial cell (EC) function and attenuate reduced uterine perfusion pressure (RUPP)-induced hypertension. RUPP was induced on day 14 of gestation (term=21), AMPK activation was stimulated in vivo by AICAR administered i.p. (50mg/kg) twice daily. Arterial pressure (AP) and tissues were collected on day 19. Human derived trophoblast cells were cultured in physiologic normoxic (8% O 2 ) and hypoxic (1.5% O 2 ) conditions. Angiogenic balance and EC function were assessed with an endothelial tube formation assay using human umbilical vascular endothelial cells (HUVEC) cultured for 8h with 5% serum from each treatment group. AICAR increased ( P <0.05) placental phosphorylation of AMPKα in RUPP+AICAR (0.33±0.06) compared to normal pregnant (NP), NP+A and RUPP rats (0.19±0.03 vs. 0.16±0.04 vs. 0.18±0.03). AICAR increased ( P <0.05) free plasma VEGF in the RUPP+AICAR (884±128 pg/ml) compared to NP+AICAR, NP and RUPP rats (708±179 vs. 843±52 vs. 420±75 pg/ml). EC function as assessed by tube formation was decreased by treatment with serum from RUPP vs . NP (25±2 vs. 51±7; tubes/frame; P <0.05) rats and this deficit was abrogated with serum from RUPP+AICAR rats (86±9 tubes/frame; P <0.05). RUPP hypertension was mitigated by AICAR infusion (NP 95±3; RUPP 123±2; NP+AICAR 104±3; RUPP+AICAR 101±5mmHg; P <0.05). Hypoxia increased ( P <0.05) VEGF secretion 30% by BeWo cells and this effect was augmented a further 60% ( P <0.05) by treatment with the AICAR mimetic metformin. AICAR increased levels of placental AMPK activation, increased free VEGF concentrations in plasma, restored endothelial cell function and reduced blood pressure RUPP rats but had no effect on these measures in NP control rats. These findings show AMPK activation and stimulation of VEGF with AICAR is ischemia/hypoxia dependent and may be useful for management of hypertension in pregnancy.

scholarly journals Trafficking of Kv1.4 potassium channels: interdependence of a pore region determinant and a cytoplasmic C-terminal VXXSL determinant in regulating cell-surface trafficking

2003 ◽  
Vol 375 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Jing ZHU ◽  
Itaru WATANABE ◽  
Barbara GOMEZ ◽  
William B. THORNHILL
Keyword(s):  
Cell Surface ◽  
Cell Function ◽  
Cell Signalling ◽  
Surface Protein ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Cell Surface Expression ◽  
Pore Region ◽  
Expression Levels ◽  
Protein Levels

Kv1.4 and Kv1.1 potassium channel homomers have been shown to exhibit different intracellular trafficking programmes and cell-surface expression levels in cell lines: a determinant in the pore region of Kv1.4 and Kv1.1 [Zhu, Watanabe, Gomez and Thornhill (2001) J. Biol. Chem. 276, 39419–39427] and a cytoplasmic C-terminal VXXSL determinant on Kv1.4 [Li, Takimoto and Levitan (2000) J. Biol. Chem. 275, 11597–11602] have been described, which affected trafficking and cell-surface expression levels. In the present study, we examined whether trafficking pore determinants influenced any cytoplasmic C-terminal trafficking determinant. We found that removal of VXXSL from a Kv1.4 chimaera that contained the pore of Kv1.1 did not affect cell-surface trafficking. Therefore removal of the C-terminal VXXSL of Kv1.4 inhibited protein surface levels only in the presence of the Kv1.4 pore. In contrast, truncating the cytoplasmic C-terminus of Kv1.1 or truncating a Kv1.1 chimaera with the pore of Kv1.4, had little effect on surface protein levels. Furthermore, the subregion of the Kv1.4 pore trafficking determinant that was required for the inhibitory effect of VXXSL removal was mapped to a threonine residue in the deep pore region. Therefore the Kv1.4 pore determinant affected the trafficking and cell-surface levels directed by the C-terminal VXXSL determinant. Different Kv1 trafficking programmes would affect cell-surface expression levels either positively or negatively and also cell signalling. Cells may use differential trafficking programmes of membrane proteins as a post-translational mechanism to regulate surface protein levels and cell function.

Characterization of porcine UL16-binding protein 1 endothelial cell surface expression

2008 ◽  
Vol 15 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Benjamin G. Lilienfeld ◽  
Anita Schildknecht ◽  
Lukas L. Imbach ◽  
Nicolas J. Mueller ◽  
Mårten K. J. Schneider ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Surface ◽  
Binding Protein ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Endothelial Cell Surface

scholarly journals Concomitant induction of the cell surface expression of Ia determinants and accessory cell function by a murine macrophage tumor cell line.

1982 ◽  
Vol 155 (2) ◽  
pp. 629-634 ◽  
Author(s):  
E B Walker ◽  
L L Lanier ◽  
N L Warner
Keyword(s):  
Cell Surface ◽  
Tumor Cells ◽  
Cell Function ◽  
Tumor Cell Line ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Accessory Cell ◽  
Gene Products ◽  
Region Gene ◽  
Histocompatibility Complex

This study demonstrates that an uncharacterized soluble factor produced in concanavalin A-induced rat spleen cell suspensions has the capacity to induce the increased expression of cell surface H-2K and H-2D molecules and the expression of I-region gene products on murine monocyte-macrophage lineage tumors that are not Ia positive in the absence of the factor. In parallel with induction of serologically defined Ia specificities, Ia-induced WEHI-3 macrophage tumor cells are capable of providing accessory cell function in stimulating IL-2 production by T-T hybridomas that are activated in a major histocompatibility complex-restricted, antigen-dependent fashion. The uninduced Ia-negative WEHI-3 tumor cells do not trigger a comparable response in this assay system.

scholarly journals Donor specific phenotypic variation in hiPSC cardiomyocyte-derived exosomes impacts endothelial cell function

2021 ◽  
Author(s):  
Amy Turner ◽  
Praful Aggarwal ◽  
Andrea Matter ◽  
Benjamin Olson ◽  
C. Charles Gu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Induced Pluripotent Stem Cell ◽  
Cell Interaction ◽  
Tube Formation ◽  
Left Ventricular ◽  
Endothelial Cell Function ◽  
Significant Expression ◽  
And Migration ◽  
Induced Pluripotent

Exosomes are an important mechanism of cell-cell interaction in the cardiovascular system, both in maintaining homeostasis and in stress response. Interindividual differences that alter content in exosomes may play a role in cardiovascular disease pathology. To study the effect of interindividual cardiomyocyte (CM) variation, we characterized exosomal content in phenotypically diverse human induced pluripotent stem cell-derived CMs (hiPSC-CMs). Cell lines were generated from six participants in the HyperGEN cohort: three with left ventricular hypertrophy (LVH) and three with normal left ventricular mass. Sequence analysis of the intracellular and exosomal RNA populations showed distinct expression pattern differences between hiPSC-CM lines derived from individuals with LVH and those with normal LV mass. Functional analysis of hiPSC-endothelial cells (hiPSC-ECs) treated with exosomes from both hiPSC-CM groups showed significant variation in response, including differences in tube formation, migration, and proliferation. Overall, treatment of hiPSC-ECs with exosomes resulted in significant expression changes associated with angiogenesis and endothelial cell vasculogenesis. However, the hiPSC-ECs treated with exosomes from the LVH-affected donors exhibited significantly increased proliferation but decreased tube formation and migration, suggesting angiogenic dysregulation.

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