GSE159158
Density dependent gene expression change in RAW264.7 cells stimulated without or with LPS.
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. Overall design: The analysis performed on single sample of highly dense, low dense and high dense cells treated with LPS to examine the change of gene expression in high dense cell (HD) with respect to low dense cells (LD). Alteration of gene expression after treatment with LPS to high dense cells also checked.