Density dependent gene expression change in RAW264.7 cells stimulated without or with LPS.
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ABSTRACT: Quorum sensing mechanisms that sense the density of macrophages at the site of inflammation, to initiate inflammation resolution, have recently been demonstrated as a major determinant of the inflammatory response. We observed a density-dependent increase in expression of the inflammatory tumor suppressor protein programmed cell death 4 (PDCD4) in mouse macrophage cells. Conditioned medium from high density cells upregulated PDCD4 expression, revealing the presence of a secreted factor(s) acting as a macrophage quorum sensor. Secreted gelsolin (GSN) was identified as the quorum sensor and alteration of GSN levels changed PDCD4 expression. LPS induced the expression of microRNA miR-21 which downregulated GSN expression and reversed the high density phenotype. The high density phenotype was correlated with an anti-inflammatory gene expression program, which was counteracted by inflammatory stimulus. Together, our observations establish the miR-21-GSN-PDCD4 regulatory network as a central mediator of a macrophage quorum sensing mechanism for the control of inflammatory responses.
ORGANISM(S): Mus musculus
PROVIDER: GSE159158 | GEO | 2020/10/08
REPOSITORIES: GEO
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