Downregulation of VEGF-D expression by interleukin-1β in cardiac microvascular endothelial cells is mediated by MAPKs and PKCα/ β1

Deidra Mountain, Mahipal Singh, Krishna Singh

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Interleukin-1β (IL-1β) is a proinflammatory cytokine increased in the heart following myocardial infarction. Vascular endothelial growth factors (VEGFs) are implicated in angiogenesis due to their involvement in the recruitment and proliferation of endothelial cells. Here we studied expression of VEGFs in response to IL-1β in rat cardiac microvascular endothelial cells (CMECs) and investigated the signaling pathways involved in the regulation of VEGF-D. cDNA array analysis indicated that IL-1β modulates the expression of numerous angiogenesis-related genes, notably decreasing the expression of VEGF-D, RT-PCR and Western blot analyses confirmed decreased expression of VEGF-D in response to IL-1β. IL-1β decreased the expression of VEGF-C to a lesser extent with no effects on VEGF-A or -B. Inhibition of ERK1/2, JNKs, or PKCα/β1 alone partially inhibited IL-1β-induced VEGF-D downregulation. Concurrent inhibition of ERK1/2 or JNKs and PKCα/β1 resulted in a synergistic inhibition of IL-1β-induced decreases in VEGF-D. Inhibition of ERK1/2 partially inhibited IL-1β-stimulated inactivation of GSK-3β with no effect on β-catenin levels. Inhibition of GSK-3β using SB216763 inhibited basal VEGF-D expression. We conclude that IL-1β downregulates VEGF-D expression in CMECs via the involvement of ERK1/2, JNKs, and PKCα/β1. This is the first report to indicate inhibition of VEGF-D gene expression in response to IL-1β in cardiac microvascular endothelial cells, a cell type of central interest in angiogenesis.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
JournalJournal of Cellular Physiology
Volume215
Issue number2
DOIs
StatePublished - May 1 2008
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor D
Endothelial cells
Interleukin-1
Down-Regulation
Endothelial Cells
Vascular Endothelial Growth Factors
Glycogen Synthase Kinase 3
Vascular Endothelial Growth Factor C
Catenins
Oligonucleotide Array Sequence Analysis
Gene expression
Vascular Endothelial Growth Factor A
Rats
Complementary DNA
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Downregulation of VEGF-D expression by interleukin-1β in cardiac microvascular endothelial cells is mediated by MAPKs and PKCα/ β1. / Mountain, Deidra; Singh, Mahipal; Singh, Krishna.

In: Journal of Cellular Physiology, Vol. 215, No. 2, 01.05.2008, p. 337-343.

Research output: Contribution to journalArticle

@article{7c571b26590f450f85f5728a21b61889,
title = "Downregulation of VEGF-D expression by interleukin-1β in cardiac microvascular endothelial cells is mediated by MAPKs and PKCα/ β1",
abstract = "Interleukin-1β (IL-1β) is a proinflammatory cytokine increased in the heart following myocardial infarction. Vascular endothelial growth factors (VEGFs) are implicated in angiogenesis due to their involvement in the recruitment and proliferation of endothelial cells. Here we studied expression of VEGFs in response to IL-1β in rat cardiac microvascular endothelial cells (CMECs) and investigated the signaling pathways involved in the regulation of VEGF-D. cDNA array analysis indicated that IL-1β modulates the expression of numerous angiogenesis-related genes, notably decreasing the expression of VEGF-D, RT-PCR and Western blot analyses confirmed decreased expression of VEGF-D in response to IL-1β. IL-1β decreased the expression of VEGF-C to a lesser extent with no effects on VEGF-A or -B. Inhibition of ERK1/2, JNKs, or PKCα/β1 alone partially inhibited IL-1β-induced VEGF-D downregulation. Concurrent inhibition of ERK1/2 or JNKs and PKCα/β1 resulted in a synergistic inhibition of IL-1β-induced decreases in VEGF-D. Inhibition of ERK1/2 partially inhibited IL-1β-stimulated inactivation of GSK-3β with no effect on β-catenin levels. Inhibition of GSK-3β using SB216763 inhibited basal VEGF-D expression. We conclude that IL-1β downregulates VEGF-D expression in CMECs via the involvement of ERK1/2, JNKs, and PKCα/β1. This is the first report to indicate inhibition of VEGF-D gene expression in response to IL-1β in cardiac microvascular endothelial cells, a cell type of central interest in angiogenesis.",
author = "Deidra Mountain and Mahipal Singh and Krishna Singh",
year = "2008",
month = "5",
day = "1",
doi = "10.1002/jcp.21315",
language = "English (US)",
volume = "215",
pages = "337--343",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Downregulation of VEGF-D expression by interleukin-1β in cardiac microvascular endothelial cells is mediated by MAPKs and PKCα/ β1

AU - Mountain, Deidra

AU - Singh, Mahipal

AU - Singh, Krishna

PY - 2008/5/1

Y1 - 2008/5/1

N2 - Interleukin-1β (IL-1β) is a proinflammatory cytokine increased in the heart following myocardial infarction. Vascular endothelial growth factors (VEGFs) are implicated in angiogenesis due to their involvement in the recruitment and proliferation of endothelial cells. Here we studied expression of VEGFs in response to IL-1β in rat cardiac microvascular endothelial cells (CMECs) and investigated the signaling pathways involved in the regulation of VEGF-D. cDNA array analysis indicated that IL-1β modulates the expression of numerous angiogenesis-related genes, notably decreasing the expression of VEGF-D, RT-PCR and Western blot analyses confirmed decreased expression of VEGF-D in response to IL-1β. IL-1β decreased the expression of VEGF-C to a lesser extent with no effects on VEGF-A or -B. Inhibition of ERK1/2, JNKs, or PKCα/β1 alone partially inhibited IL-1β-induced VEGF-D downregulation. Concurrent inhibition of ERK1/2 or JNKs and PKCα/β1 resulted in a synergistic inhibition of IL-1β-induced decreases in VEGF-D. Inhibition of ERK1/2 partially inhibited IL-1β-stimulated inactivation of GSK-3β with no effect on β-catenin levels. Inhibition of GSK-3β using SB216763 inhibited basal VEGF-D expression. We conclude that IL-1β downregulates VEGF-D expression in CMECs via the involvement of ERK1/2, JNKs, and PKCα/β1. This is the first report to indicate inhibition of VEGF-D gene expression in response to IL-1β in cardiac microvascular endothelial cells, a cell type of central interest in angiogenesis.

AB - Interleukin-1β (IL-1β) is a proinflammatory cytokine increased in the heart following myocardial infarction. Vascular endothelial growth factors (VEGFs) are implicated in angiogenesis due to their involvement in the recruitment and proliferation of endothelial cells. Here we studied expression of VEGFs in response to IL-1β in rat cardiac microvascular endothelial cells (CMECs) and investigated the signaling pathways involved in the regulation of VEGF-D. cDNA array analysis indicated that IL-1β modulates the expression of numerous angiogenesis-related genes, notably decreasing the expression of VEGF-D, RT-PCR and Western blot analyses confirmed decreased expression of VEGF-D in response to IL-1β. IL-1β decreased the expression of VEGF-C to a lesser extent with no effects on VEGF-A or -B. Inhibition of ERK1/2, JNKs, or PKCα/β1 alone partially inhibited IL-1β-induced VEGF-D downregulation. Concurrent inhibition of ERK1/2 or JNKs and PKCα/β1 resulted in a synergistic inhibition of IL-1β-induced decreases in VEGF-D. Inhibition of ERK1/2 partially inhibited IL-1β-stimulated inactivation of GSK-3β with no effect on β-catenin levels. Inhibition of GSK-3β using SB216763 inhibited basal VEGF-D expression. We conclude that IL-1β downregulates VEGF-D expression in CMECs via the involvement of ERK1/2, JNKs, and PKCα/β1. This is the first report to indicate inhibition of VEGF-D gene expression in response to IL-1β in cardiac microvascular endothelial cells, a cell type of central interest in angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=40949117155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40949117155&partnerID=8YFLogxK

U2 - 10.1002/jcp.21315

DO - 10.1002/jcp.21315

M3 - Article

VL - 215

SP - 337

EP - 343

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -