ArticleScientific reports2015
NFAT isoforms play distinct roles in TNFα-induced retinal leukostasis.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Establishment of CD34 + hematopoietic stem cell-derived xenograft model of hyperleukocytic acute myeloid leukemia.BMC cancer · 2025Article
- Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina.Cellular signalling · 2024Article
- Genetic heterogeneity of liver cancer stem cells.Anatomy & cell biology · 2023Article
- Effect of cytokine-induced alterations in extracellular matrix composition on diabetic retinopathy-relevant endothelial cell behaviors.Scientific reports · 2022Article
- Characterization and Validation of In Vitro and In Vivo Models to Investigate TNF-α-Induced Inflammation in Retinal Diseases.Translational vision science & technology · 2022Article
- Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Vascular Health Triad in Humans With Hypertension-Not the Usual Suspects.Frontiers in physiology · 2021Review
- The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.Experimental eye research · 2020Article
- A hospital based retrospective study of factors influencing therapeutic leukapheresis in patients presenting with hyperleukocytic leukaemia.Scientific reports · 2018Article
- Epoxygenated Fatty Acids Inhibit Retinal Vascular Inflammation.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The objective of this study was to determine the role of individual NFAT isoforms in TNFα-induced retinal leukostasis. To this end, human retinal microvascular endothelial cells (HRMEC) transfected with siRNA targeting individual NFAT isoforms were treated with TNFα, and qRT-PCR was used to examine the contribution of each isoform to the TNFα-induced upregulation of leukocyte adhesion proteins. This showed that NFATc1 siRNA increased ICAM1 expression, NFATc2 siRNA reduced CX3CL1, VCAM1, SELE, and ICAM1 expression, NFATc3 siRNA increased CX3CL1 and SELE expression, and NFATc4 siRNA reduced SELE expression. Transfected HRMEC monolayers were also treated with TNFα and assayed using a parallel plate flow chamber, and both NFATc2 and NFATc4 knockdown reduced TNFα-induced cell adhesion. The effect of isoform-specific knockdown on TNFα-induced cytokine production was also measured using protein ELISAs and conditioned cell culture medium, and showed that NFATc4 siRNA reduced CXCL10, CXCL11, and MCP-1 protein levels. Lastly, the CN/NFAT-signaling inhibitor INCA-6 was shown to reduce TNFα-induced retinal leukostasis in vivo. Together, these studies show a clear role for NFAT-signaling in TNFα-induced retinal leukostasis, and identify NFATc2 and NFATc4 as potentially valuable therapeutic targets for treating retinopathies in which TNFα plays a pathogenic role.
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