Hypoxia/ischemia promotes CXCL10 expression in cardiac microvascular endothelial cells by NFkB activation

Jing Bo Xia, Guang Hui Liu, Zhuo Ying Chen, Cheng Zhou Mao, Deng Cheng Zhou, Hai Yan Wu, Kyusang Park, Hui Zhao, Soo-Ki Kim, Dong Qing Cai, Xu Feng Qi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

CXCL10, the chemokine with potent chemotactic activity on immune cells and other non-immune cells expressing its receptor CXCR3, has been demonstrated to involve in myocardial infarction, which was resulted from hypoxia/ischemia. The cardiac microvascular endothelial cells (CMECs) are the first cell type which is implicated by hypoxia/ischemia. However, the potential molecular mechanism by which hypoxia/ischemia regulates the expression of CXCL10 in CMECs remains unclear. In the present study, the expression of CXCL10 was firstly examined by real-time PCR and ELISA analysis. Several potential binding sites (BS) for transcription factors including NF-kappaB (NFkB), HIF1 alpha (HIF1α) and FoxO3a were identified in the promoter region of CXCL10 gene from -2000 bp to -1 bp using bioinformatics software. Luciferase reporter gene vectors for CXCL10 promoter and for activation of above transcription factors were constructed. The activation of NFkB, hypoxia-inducible transcription factor-1 alpha (HIF-1α) and FoxO3a was also analyzed by Western blotting. It was shown that the production of CXCL10 in CMECs was significantly increased by hypoxia/ischemia treatment, in parallel with the activation of CXCL10 promoter examined by reporter gene vector system. Furthermore, transcription factors including NFkB, HIF1α and FoxO3a were activated by hypoxia/ischemia in CMECs. However, over-expression of NFkB, but not that of HIF1α or FoxO3a, significantly promoted the activation of CXCL10 promoter reporter gene. These findings indicated that CXCL10 production in CMECs was significantly increased by hypoxia/ischemia, at least in part, through activation of NFkB pathway and subsequently binding to CXCL10 promoter, finally promoted the transcription of CXCL10 gene.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalCytokine
Volume81
DOIs
Publication statusPublished - 2016 May 1

Fingerprint

NF-kappa B
Endothelial cells
Ischemia
Endothelial Cells
Genes
Chemical activation
Transcription Factors
Reporter Genes
CXCR3 Receptors
Chemokine CXCL10
Hypoxia-Inducible Factor 1
Transcription
Bioinformatics
Luciferases
Genetic Promoter Regions
Computational Biology
Binding Sites
Cells
Hypoxia
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Xia, J. B., Liu, G. H., Chen, Z. Y., Mao, C. Z., Zhou, D. C., Wu, H. Y., ... Qi, X. F. (2016). Hypoxia/ischemia promotes CXCL10 expression in cardiac microvascular endothelial cells by NFkB activation. Cytokine, 81, 63-70. https://doi.org/10.1016/j.cyto.2016.02.007
Xia, Jing Bo ; Liu, Guang Hui ; Chen, Zhuo Ying ; Mao, Cheng Zhou ; Zhou, Deng Cheng ; Wu, Hai Yan ; Park, Kyusang ; Zhao, Hui ; Kim, Soo-Ki ; Cai, Dong Qing ; Qi, Xu Feng. / Hypoxia/ischemia promotes CXCL10 expression in cardiac microvascular endothelial cells by NFkB activation. In: Cytokine. 2016 ; Vol. 81. pp. 63-70.
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abstract = "CXCL10, the chemokine with potent chemotactic activity on immune cells and other non-immune cells expressing its receptor CXCR3, has been demonstrated to involve in myocardial infarction, which was resulted from hypoxia/ischemia. The cardiac microvascular endothelial cells (CMECs) are the first cell type which is implicated by hypoxia/ischemia. However, the potential molecular mechanism by which hypoxia/ischemia regulates the expression of CXCL10 in CMECs remains unclear. In the present study, the expression of CXCL10 was firstly examined by real-time PCR and ELISA analysis. Several potential binding sites (BS) for transcription factors including NF-kappaB (NFkB), HIF1 alpha (HIF1α) and FoxO3a were identified in the promoter region of CXCL10 gene from -2000 bp to -1 bp using bioinformatics software. Luciferase reporter gene vectors for CXCL10 promoter and for activation of above transcription factors were constructed. The activation of NFkB, hypoxia-inducible transcription factor-1 alpha (HIF-1α) and FoxO3a was also analyzed by Western blotting. It was shown that the production of CXCL10 in CMECs was significantly increased by hypoxia/ischemia treatment, in parallel with the activation of CXCL10 promoter examined by reporter gene vector system. Furthermore, transcription factors including NFkB, HIF1α and FoxO3a were activated by hypoxia/ischemia in CMECs. However, over-expression of NFkB, but not that of HIF1α or FoxO3a, significantly promoted the activation of CXCL10 promoter reporter gene. These findings indicated that CXCL10 production in CMECs was significantly increased by hypoxia/ischemia, at least in part, through activation of NFkB pathway and subsequently binding to CXCL10 promoter, finally promoted the transcription of CXCL10 gene.",
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Hypoxia/ischemia promotes CXCL10 expression in cardiac microvascular endothelial cells by NFkB activation. / Xia, Jing Bo; Liu, Guang Hui; Chen, Zhuo Ying; Mao, Cheng Zhou; Zhou, Deng Cheng; Wu, Hai Yan; Park, Kyusang; Zhao, Hui; Kim, Soo-Ki; Cai, Dong Qing; Qi, Xu Feng.

In: Cytokine, Vol. 81, 01.05.2016, p. 63-70.

Research output: Contribution to journalArticle

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AU - Xia, Jing Bo

AU - Liu, Guang Hui

AU - Chen, Zhuo Ying

AU - Mao, Cheng Zhou

AU - Zhou, Deng Cheng

AU - Wu, Hai Yan

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AU - Qi, Xu Feng

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