scholarly journals Hsp90 inhibition suppresses LPS‐mediated NFkB target gene expression without affecting NFkB nuclear translocation in human lung microvascular endothelial cells

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Gagan S Thangjam ◽  
Atul D Joshi ◽  
Connie Snead ◽  
Chris L Wallace ◽  
John D Catravas
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Target Gene ◽  
Human Lung ◽  
Nuclear Translocation ◽  
Microvascular Endothelial Cells ◽  
Hsp90 Inhibition ◽  
Target Gene Expression ◽  
Microvascular Endothelial

scholarly journals Hantavirus Infection Induces the Expression of RANTES and IP-10 without Causing Increased Permeability in Human Lung Microvascular Endothelial Cells

2001 ◽  
Vol 75 (13) ◽  
pp. 6070-6085 ◽  
Author(s):  
J. Bruce Sundstrom ◽  
Laura K. McMullan ◽  
Christina F. Spiropoulou ◽  
W. Craig Hooper ◽  
Aftab A. Ansari ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Permeability ◽  
Human Lung ◽  
Nuclear Translocation ◽  
Microvascular Endothelial Cells ◽  
Hantavirus Infection ◽  
Induced Expression ◽  
Synergistic Enhancement ◽  
Ifn Γ ◽  
Microvascular Endothelial

ABSTRACT Sin Nombre virus (SNV) and Hantaan virus (HTN) infect endothelial cells and are associated with different patterns of increased vascular permeability during human disease. It is thought that such patterns of increased vascular permeability are a consequence of endothelial activation and subsequent dysfunction mediated by differential immune responses to hantavirus infection. In this study, the ability of hantavirus to directly induce activation of human lung microvascular endothelial cells (HMVEC-Ls) was examined. No virus-specific modulation in the constitutive or cytokine-induced expression of cellular adhesion molecules (CD40, CD54, CD61, CD62E, CD62P, CD106, and major histocompatibility complex classes I and II) or in cytokines and chemokines (eotaxin, tumor necrosis factor alpha, interleukin 1β [IL-1β], IL-6, IL-8, MCP-1, MIP-1α, and MIP-1β) was detected at either the protein or message level in hantavirus-infected HMVEC-Ls. Furthermore, no virus-specific enhancement of paracellular or transcellular permeability or changes in the organization and distribution of endothelial intercellular junctional proteins was observed. However, infection with either HTN or SNV resulted in detectable levels of the chemokines RANTES and IP-10 (the 10-kDa interferon-inducible protein) in HMVEC-Ls within 72 h and was associated with nuclear translocation of interferon regulatory factor 3 (IRF-3) and IRF-7. Gamma interferon (IFN-γ)-induced expression of RANTES and IP-10 could also be detected in uninfected HMVEC-Ls and was associated with nuclear translocation of IRF-1 and IRF-3. Treatment of hantavirus-infected HMVEC-Ls with IFN-γ for 24 h resulted in a synergistic enhancement in the expression of both RANTES and IP-10 and was associated with nuclear translocation of IRF-1, IRF-3, IRF-7, and NF-κB p65. These results reveal a possible mechanism by which hantavirus infection and a TH1 immune response can cooperate to synergistically enhance chemokine expression by HMVEC-Ls and trigger immune-mediated increases in vascular permeability.

scholarly journals Hsp90 inhibition suppresses NF-κB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells

2016 ◽  
Vol 310 (10) ◽  
pp. L964-L974 ◽  
Author(s):  
Gagan S. Thangjam ◽  
Charalampos Birmpas ◽  
Nektarios Barabutis ◽  
Betsy W. Gregory ◽  
Mary Ann Clemens ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcriptional Activation ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Gene Promoter ◽  
Microvascular Endothelial Cells ◽  
Mrna Induction ◽  
Target Gene Promoter ◽  
Microvascular Endothelial

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation of Sirt-2 protein expression. Furthermore, this process is independent of NF-κB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-κB target gene promoter via interaction with core histones. Upon inflammatory challenge, chromatin remodeling and core histone H3 displacement from the promoter region removes Sirt-2 and allows NF-κB/coactivator recruitment essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have important implications in pulmonary inflammation.

Gene expression profiles of glucose toxicity-exposed islet microvascular endothelial cells

2018 ◽  
Vol 25 (4) ◽  
pp. e12450 ◽  
Author(s):  
Mingming Liu ◽  
Wenbao Lu ◽  
Qunxing Hou ◽  
Bing Wang ◽  
Youming Sheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Microvascular Endothelial Cells ◽  
Glucose Toxicity ◽  
Microvascular Endothelial

scholarly journals MicroRNA-Regulated Rickettsial Invasion into Host Endothelium via Fibroblast Growth Factor 2 and Its Receptor FGFR1

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 240 ◽  
Author(s):  
Abha Sahni ◽  
Hema Narra ◽  
Jignesh Patel ◽  
Sanjeev Sahni
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Host Cells ◽  
Microvascular Endothelial Cells ◽  
Target Cells ◽  
Fibroblast Growth ◽  
Wide Range ◽  
Microvascular Endothelial

Microvascular endothelial cells (ECs) represent the primary target cells during human rickettsioses and respond to infection via the activation of immediate–early signaling cascades and the resultant induction of gene expression. As small noncoding RNAs dispersed throughout the genome, microRNAs (miRNAs) regulate gene expression post-transcriptionally to govern a wide range of biological processes. Based on our recent findings demonstrating the involvement of fibroblast growth factor receptor 1 (FGFR1) in facilitating rickettsial invasion into host cells and published reports suggesting miR-424 and miR-503 as regulators of FGF2/FGFR1, we measured the expression of miR-424 and miR-503 during R. conorii infection of human dermal microvascular endothelial cells (HMECs). Our results revealed a significant decrease in miR-424 and miR-503 expression in apparent correlation with increased expression of FGF2 and FGFR1. Considering the established phenomenon of endothelial heterogeneity and pulmonary and cerebral edema as the prominent pathogenic features of rickettsial infections, and significant pathogen burden in the lungs and brain in established mouse models of disease, we next quantified miR-424 and miR-503 expression in pulmonary and cerebral microvascular ECs. Again, R. conorii infection dramatically downregulated both miRNAs in these tissue-specific ECs as early as 30 min post-infection in correlation with higher FGF2/FGFR1 expression. Changes in the expression of both miRNAs and FGF2/FGFR1 were next confirmed in a mouse model of R. conorii infection. Furthermore, miR-424 overexpression via transfection of a mimic into host ECs reduced the expression of FGF2/FGFR1 and gave a corresponding decrease in R. conorii invasion, while an inhibitor of miR-424 had the expected opposite effect. Together, these findings implicate the rickettsial manipulation of host gene expression via regulatory miRNAs to ensure efficient cellular entry as the critical requirement to establish intracellular infection.

W1594 Importins α1 and α3 Regulate VEGF Gene Expression and Angiogenesis in Gastric Mucosal Microvascular Endothelial Cells.

2009 ◽  
Vol 136 (5) ◽  
pp. A-698-A-699
Author(s):  
Amrita Ahluwalia ◽  
Xiaoming Deng ◽  
Vipal Gandhi ◽  
Sushrut S. Thiruvengadam ◽  
Andrzej S. Tarnawski
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Microvascular Endothelial Cells ◽  
Vegf Gene ◽  
Microvascular Endothelial
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