Premium
CAM/CAMKII‐dependent survival signaling in bone marrow derived macrophages
Author(s) -
Tano Jean-Yves Kouame,
Vazquez Guillermo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb548
Subject(s) - protein kinase b , pi3k/akt/mtor pathway , p38 mitogen activated protein kinases , macrophage , ly294002 , tunel assay , mapk/erk pathway , signal transduction , cancer research , apoptosis , microbiology and biotechnology , phosphorylation , bone marrow , chemistry , medicine , immunology , biology , in vitro , biochemistry
The balance between macrophage survival and apoptosis is crucial at all stages of atherosclerotic lesion development. We here report that survival mechanisms recently described by us in THP‐1 derived macrophages, are also operational in primary cultures of bone marrow derived macrophages (BMDMs). Similarly to TNF, treatment of BMDMs with oxidized‐LDL results in activation of the canonical survival pathways PI3K/AKT and NFkB as well as the p38α MAPK route. We used pharmacological maneuvers, western blotting and TUNEL to examine the potential mechanisms that may contribute to regulate these survival signaling routes. Treatment with calmodulin (CAM) and CAM‐dependent kinase II (CAMKII) inhibitors significantly reduced activation of AKT and IkBα, and this was positively correlated with an increase in the number of TUNEL positive cells. Surprisingly, inhibition of PI3K using LY294002 markedly reduced not only AKT activation, but also the phosphorylation of IkBα and p38α suggesting a role of PI3K/AKT as a signaling node from which other survival pathways are activated. Altogether, these results suggest that in an inflammatory setting, macrophages trigger compensatory survival mechanisms that involve activation of the PI3K/AKT, NFkB and p38 MAPK routes in a CAM/CAMKII dependent manner. Supported by the NIH R01‐HL111877‐01