The Wnt-signaling pathway plays a critical role in directing cell fate during embryogenesis. Several lines of evidence also suggest a role in inflammatory processes. Here, we analyzed whether Wnt signaling plays a role in leukocyte inflammatory responses. Monocytes from healthy donors expressed different Frizzled receptors, which are ligands for the Wnt molecules. Activation of the Wnt/beta-catenin pathway by LiCl or Wnt3a increased beta-catenin protein levels in monocytes but not in granulocytes. It is interesting that the activation of Wnt/beta-catenin signaling via Wnt3a in monocytes resulted in a decrease in migration through an endothelial layer (human dermal microvascular endothelial cell-1). Further experiments revealed that the decrease in transendothelial migration was associated with specific monocyte adherence to endothelial cells after Wnt exposure. The specificity was verified by a lack of Wnt3a-induced adhesion to fibronectin, laminin, or collagen compared with endothelial interaction. Analysis of the distribution of beta-catenin revealed a Wnt3a-induced increase of beta-catenin in the cytoplasm. Wnt3a exposure did not result in any activation of the classical Wnt-target gene c-myc or a Wnt-target gene involved in cell adhesion (Connexin43). Our study implicates for the first time a role of canonical Wnt signaling in inflammatory processes in monocytes.

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http://dx.doi.org/10.1189/jlb.0905539DOI Listing

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