Annexin A1 Released from Apoptotic Cells Acts Through Formyl Peptide Receptors to Dampen Inflammatory Monocyte Activation Via JAK/STAT/SOCS Signalling

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2011 Jan 22

PMID 21254404

Citations 40

Authors

Danute Pupjalis

Julia Goetsch

Diane J Kottas

Volker Gerke

Ursula Rescher

Affiliations

Soon will be listed here.

Abstract

The immunosuppressive effects of apoptotic cells involve inhibition of pro-inflammatory cytokine release and establishment of an anti-inflammatory cytokine profile, thus limiting the degree of inflammation and promoting resolution. We report here that this is in part mediated by the release of the anti-inflammatory mediator annexin A1 from apoptotic cells and the functional activation of annexin A1 receptors of the formyl peptide receptor (FPR) family on target cells. Supernatants from apoptotic neutrophils or the annexin A1 peptidomimetic Ac2-26 significantly reduced IL-6 signalling and the release of TNF-α from endotoxin-challenged monocytes. Ac2-26 activated STAT3 in a JAK-dependent manner, resulting in upregulated SOCS3 levels, and depletion of SOCS3 reversed the Ac2-26-mediated inhibition of IL-6 signalling. This identifies annexin A1 as part of the anti-inflammatory pattern of apoptotic cells and links the activation of FPRs to established signalling pathways triggering anti-inflammatory responses.

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