期刊
EXPERIMENTAL CELL RESEARCH
卷 341, 期 2, 页码 225-236出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2016.02.004
关键词
Macrophage; RhoA; ROCK1; Caspase-3; Actin; Hummingbird phenotype
资金
- Williams Stamps Farish Fund
- Donald D. Hammill Foundation
The macrophages have different subtypes with different functions in immune response and disease. It has been generally accepted that M1 macrophages are responsible for stimulation of immune system and inflammation while M2 macrophages play a role in tissue repair. Irrespective of the type, macrophage functions depend on actin cytoskeleton, which is under the control of small GTPase RhoA pathway and its downstream effector ROCK1. We generated RhoA-deleted macrophages and compared the effect of RhoA deletion on M0, M1 and M2 macrophage phenotype. Our studies showed that, unexpectedly, the RhoA deletion did not eliminate macrophage ROCK1 expression and increased ROCK1 activity. The RhoA deletion effect on macrophage phenotype, structure and polarity was different for each subtype. Moreover, our study indicates that the up-regulation of ROCK1 activity in RhoA-deleted macrophages and macrophage phenotype/polarity are dependent on non-apoptotic Caspase-3 and are sensitive to Caspase-3 inhibition. These novel findings will revise/complement our understanding of RhoA pathway regulation of cell structure and polarity. (C) 2016 Elsevier Inc. All rights reserved.
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