Annexin A1 released from apoptotic cells acts through formyl peptide receptors to dampen inflammatory monocyte activation via JAK/STAT/SOCS signalling.
Bottom Line: 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.
Affiliation: Centre for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Centre, Institute of Medical Biochemistry, University of Muenster, Muenster, Germany.Show MeSH
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Mentions: We first examined the effects of mediators released by apoptotic human neutrophils on the lipopolysaccharide (LPS, Calbiochem)-induced TNF-α release in monocytes. Human monocytes were pre-treated with culture supernatants obtained from apoptotic neutrophils, challenged with LPS and the levels of released TNF-α were then determined by enzyme-linked immunosorbent assay (ELISA; Immunotools). As expected, a substantial TNF-α release occurred in LPS-stimulated monocytes. However, when monocytes were pre-treated with apoptotic supernatant, a significant decrease in the amount of released TNF-α was observed (Fig 1A).
Affiliation: Centre for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Centre, Institute of Medical Biochemistry, University of Muenster, Muenster, Germany.