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J Leukoc Biol. 2007 Dec;82(6):1592-604. Epub 2007 Sep 12.

Transcriptional profiling of human monocytes reveals complex changes in the expression pattern of inflammation-related genes in response to the annexin A1-derived peptide Ac1-25.

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  • 1Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Centre, University of Muenster, Muenster, Germany.

Abstract

Annexin A1 is a glucocorticoid-regulated, anti-inflammatory protein, which plays an important role as an endogenous regulator of the inflammatory response. Many of these anti-inflammatory properties are retained in the N-terminal annexin A1 peptide Ac1-25, which is released from the full-length protein by a neutrophil elastase. To elucidate whether the anti-inflammatory activity of the bioactive peptide is solely a result of immediate post-translational effects, which include the shedding of L-selectin or also involve transcriptional changes affecting leukocyte function, we recorded global gene expression changes in human monocytes stimulated with exogenously applied Ac1-25. Applying stringent selection criteria, we show that approximately 100 genes are up-regulated, and approximately 230 are down-regulated by a factor of at least two in the Ac1-25-treated monocytes. It is important that the profiling reveals that Ac1-25 induces an anti-inflammatory phenotype by down-regulating proinflammatory and up-regulating anti-inflammatory mediators. These effects, elicited by exogenously applied Ac1-25, depend, to different extents, on ERK1/2 and p38 signaling pathways. This identifies the annexin A1 N-terminal peptide as a stimulus, eliciting not only short-term, post-translational effects in human monocytes but also transcriptional changes, defining a more anti-inflammatory profile.

PMID:
17855500
[PubMed - indexed for MEDLINE]
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