Quorum Sensing by Gelsolin Regulates Programmed Cell Death 4 Expression and a Density-Dependent Phenotype in Macrophages.

Quorum-sensing mechanisms that sense the density of immune cells 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-sensing autoinducer. Alteration of GSN levels changed PDCD4 expression and the density-dependent phenotype of cells. LPS induced the expression of microRNA miR-21, which downregulated both GSN and PDCD4 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 crucial mediator of a macrophage quorum-sensing mechanism for the control of inflammatory responses. Copyright © 2021 by The American Association of Immunologists, Inc.

Citation

Reshma Kumari Sharma, Binita Goswami, Sukhen Das Mandal, Abhishek Guha, Belinda Willard, Partho Sarothi Ray. Quorum Sensing by Gelsolin Regulates Programmed Cell Death 4 Expression and a Density-Dependent Phenotype in Macrophages. Journal of immunology (Baltimore, Md. : 1950). 2021 Sep 01;207(5):1250-1264

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PMID: 34362832

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