Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs

Introduction: Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/beta-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/beta-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods: The Wnt/beta-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naive and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results: The activation of Wnt/beta-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naive state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/beta-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/beta-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion: These results suggest a mechanism by which Wnt/beta-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.

Automated summary

The Wnt/beta-catenin signaling pathway modulates macrophage polarization in an inflammatory state by regulating the Stat signaling pathway.