Mouse macrophage polarity and ROCK1 activity depend on RhoA and non-apoptotic Caspase 3.

Abstract:

: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.

journal_name

Exp Cell Res

authors

Liu Y,Minze LJ,Mumma L,Li XC,Ghobrial RM,Kloc M

doi

10.1016/j.yexcr.2016.02.004

subject

Has Abstract

pub_date

2016-02-15 00:00:00

pages

225-36

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(16)30027-1

journal_volume

341

pub_type

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