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Interleukin-1 Beta Increases Activity of Human Endothelial Progenitor Cells: Involvement of PI3K-Akt Signaling Pathway

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Abstract

Interleukin-1β (IL-1β) is a multifunctional proinflammatory cytokine upregulated in acute phase of heart ischemic disease. Controversial effects of IL-1β have been demonstrated on endothelial progenitor cells (EPCs) functional activity. The aim of this study was to investigate the in vitro effect of IL-1β on activity of human origin EPCs and the possible mechanism involved. EPCs were isolated from peripheral blood of healthy volunteers without cardiovascular risk factors and characterized. After ex vivo cultivation, EPCs were stimulated with a series of final concentrations (0, 0.1, 1, and 10 ng/ml) of IL-1β for 24 h. In some other experiments, EPCs were pretreated with 10 μM LY294002 (Akt inhibitor) for 30 min and then stimulated with 1 ng/ml IL-1β for 24 h. Cell proliferation, apoptosis, adhesion, and migration were determined, respectively, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin V/propidium iodide binding assay, adhesion assay, and transwell migration assay. In addition, the vascular endothelial vascular growth factor-A (VEGF-A) production has been examined using quantitative real-time RT-PCR and ELISA assay. Furthermore, the total and phosphorylation level of Akt was determined by Western blot. IL-1β significantly stimulated EPC proliferation, migration, and adhesion and upregulated the angiogenic growth factor VEGF-A at mRNA and protein level, while exerted no influence on cell apoptosis. However, pretreatment with LY294002 significantly diminished IL-1β-induced proliferation, migration, adhesion, and VEGF-A production. One nanogram per milliliter IL-1β for 15 min activated phosphorylation of Akt. These results suggest a potent role for IL-1β in upregulating EPCs functions. The phosphatidyl-inositol-3-kinase-Akt signaling pathway could be involved in the regulation of EPCs functions induced by IL-1β.

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Abbreviations

EPCs:

Endothelial progenitor cells.

HIF-1α:

Hypoxia-inducible factor 1α.

IL-1β:

Interleukin-1 beta.

M199:

Medium 199.

MNCs:

Mononuclear cells.

MTT:

3-(4 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide.

PBS:

Phosphate-buffered saline.

VEGF:

Endothelial vascular growth factor.

VEGF-A:

Endothelial vascular growth factor-A.

PI3K:

Phosphatidylinositol 3-kinase

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Acknowledgments

We thank Jun- Hui Zhu and Mohamed S. Draz for the critically reviewing the manuscript.

Conflicts of Interest

The authors have no conflicting financial interests.

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Authors and Affiliations

  1. Department of Cardiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, 310003, Zhejiang, People’s Republic of China

    Lin Yang, **ao-Gang Guo, **-**u Yang, Wen-**g Zhou & Fu-Rong Zhang

  2. Department of Cardiology, Zhejiang Hospital, Hangzhou, 310013, People’s Republic of China

    Chang-Qing Du

  3. Department of Cardiology, Sir Run Run Shaw Hospital, the Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, 310016, China

    Dong-Mei Jiang

  4. Department of Cardiology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China

    Bo Li

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  1. Lin Yang
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Correspondence to Fu-Rong Zhang.

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Yang, L., Guo, XG., Du, CQ. et al. Interleukin-1 Beta Increases Activity of Human Endothelial Progenitor Cells: Involvement of PI3K-Akt Signaling Pathway. Inflammation 35, 1242–1250 (2012). https://doi.org/10.1007/s10753-012-9434-9

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