Wnt5a activates THP-1 monocytic cells via a β-catenin-independent pathway involving JNK and NF-κB activation

Cytokine. 2012 Oct;60(1):242-8. doi: 10.1016/j.cyto.2012.06.013. Epub 2012 Jul 2.

Abstract

Wnt5a has been implicated in the activation of macrophages. However, the profile and mechanism of downstream regulation has not been characterized. In this study, we have investigated the regulation of Wnt5a-induced activation in monocytic THP-1 cells. Wnt5a activated THP-1 cells, enhancing adhesion to endothelial cells. Hypoxia induced the production of Wnt5a, suggesting a role in the hypoxia-induced activation of macrophages. Wnt5a induced the expression of various pro-inflammatory cytokines and inflammatory mediators, particularly IL8 and CXCL2, suggesting a major role in the secretion of CXC chemokines by macrophages. Wnt5a induced JNK phosphorylation and NF-κB activation via β-catenin-independent signaling. Interestingly, SP600125, a specific inhibitor of JNK, inhibited Wnt5a-induced activation of NF-κB, supporting JNK-dependent NF-κB activation. Our data suggest that Wnt5a activates monocytic cells via JNK and NF-κB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Hypoxia
  • Cell Line, Tumor
  • Chemokine CXCL2 / genetics
  • Chemokine CXCL2 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / pharmacology*
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Wnt Proteins / genetics
  • Wnt Proteins / pharmacology*
  • Wnt-5a Protein
  • beta Catenin / metabolism*

Substances

  • Anthracenes
  • Chemokine CXCL2
  • Cytokines
  • Inflammation Mediators
  • Interleukin-8
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • WNT5A protein, human
  • Wnt Proteins
  • Wnt-5a Protein
  • beta Catenin
  • pyrazolanthrone
  • JNK Mitogen-Activated Protein Kinases