Journal
EMBO MOLECULAR MEDICINE
Volume 3, Issue 2, Pages 102-114Publisher
WILEY
DOI: 10.1002/emmm.201000113
Keywords
annexins; apoptosis; inflammation; innate immunity; signalling
Categories
Funding
- Interdisciplinary Clinical Research Centre (IZKF) [RE2/033/04]
- Innovative Medical Research of the University of Munster Medical School [RE120522]
- German Research Foundation (DFG) [RE2611-1]
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The immunosuppressive effects of apoptotic cells involve inhibition of proinflammatory 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-alpha 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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