Title

ERBB signaling attenuates proinflammatory activation of nonclassical monocytes.

Document Type

Article

Publication Date

5-1-2017

Institution/Department

MMCRI

Journal Title

American journal of physiology. Heart and circulatory physiology.

MeSH Headings

ErbB Receptors, Female, Humans, In Vitro Techniques, Inflammation, Macrophage Activation, Male, Middle Aged, Monocytes, Neuregulin-1, Phosphatidylinositol 3-Kinases, Receptor, ErbB-2, Receptor, ErbB-3, Recombinant Proteins, Signal Transduction, Tumor Necrosis Factor-alpha

Abstract

Immune activation in chronic systolic heart failure (HF) correlates with disease severity and prognosis. Recombinant neuregulin-1 (rNRG-1) is being developed as a possible therapy for HF, based on the activation of ERBB receptors in cardiac cells. Work in animal models of HF led us to hypothesize that there may be direct effects of NRG-1 on immune system activation and inflammation. We investigated the expression of ERBB receptors and the effect of rNRG-1 isoform glial growth factor 2 (GGF2) in subpopulations of peripheral blood mononuclear cells (PB MNCs) in subjects with HF. We found that human monocytes express both ERBB2 and ERBB3 receptors, with high interindividual variability among subjects. Monocyte surface ERBB3 and TNF-α mRNA expression were inversely correlated in subjects with HF but not in human subjects without HF. GGF2 activation of ERBB signaling ex vivo inhibited LPS-induced TNF-α production, specifically in the CD14

ISSN

1522-1539

First Page

907

Last Page

907

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