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EGCG induces G-CSF expression and neutrophilia in experimental sepsis

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Abstract

A major green tea component, epigallocatechin-3-gallate (EGCG), has been proven protective against lethal sepsis in experimental setting, but its protective mechanisms remain incompletely understood. Here, we provide evidence to support EGCG’s capacities in stimulating G-CSF production and neutrophilia in vivo. In an animal model of sepsis, EGCG significantly elevated peritoneal levels of G-CSF and several chemokines (e.g., MCP-1/CCL2 and MIP-1γ/CCL9), and consequently increased peritoneal neutrophil numbers (neutrophilia) at a late stage. In vitro, EGCG divergently affected HMGB1-mediated production of several chemokines: reducing CXCL15 and RANTES/CCL5, but elevating G-CSF and MIP-1α/CCL3 production by peritoneal macrophages. Similarly, it significantly induced the expression and secretion of G-CSF and MIP-1α/CCL3 in human peripheral blood mononuclear cells. Based on our preliminary data, it may be important to search for anti-inflammatory and G-CSF-stimulating agents for the clinical management of inflammatory diseases.

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Abbreviations

CLP:

Cecal ligation and puncture

EGCG:

Epigallocatechin-3-gallate

G-CSF:

Granulocyte colony-stimulating factor

HMGB1:

High-mobility group box 1

MIP-1:

Macrophage inflammatory protein-1

TLR:

Toll-like receptor

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Acknowledgments

This work was supported by Grants from the National Center of Complementary and Alternative Medicine (NCCIH, R01AT05076) and the National Institute of General Medical Sciences (NIGMS, R01GM063075).

Author contributions

H.W., W.L., R.W., S.Z., and J.D. designed the study; W.L., S. Z., A.W., and R.W. performed the experiments; J.L. provided purified recombinant HMGB1; H.W. analyzed data and wrote the manuscript.

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    Authors and Affiliations

    1. Department of Emergency Medicine, North Shore University Hospital, 350 Community Drive, Manhasset, NY, 11030, USA

      Wei Li, Andrew H. Wu, Shu Zhu, John D’Angelo & Haichao Wang

    2. The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA

      Wei Li, Andrew H. Wu, Shu Zhu, Jianhua Li, Rong Wu & Haichao Wang

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    1. Wei Li
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    Correspondence to Haichao Wang.

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    Wei Li, Andrew H. Wu and Shu Zhu have contributed equally to this work.

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    Li, W., Wu, A.H., Zhu, S. et al. EGCG induces G-CSF expression and neutrophilia in experimental sepsis. Immunol Res 63, 144–152 (2015). https://doi.org/10.1007/s12026-015-8681-x

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