M-CSF induces monocyte survival by activating NF-?B p65 phosphorylation at Ser276 via protein kinase C.

ABSTRACT: Macrophage colony-stimulating factor (M-CSF) promotes mononuclear phagocyte survival and proliferation. The transcription factor Nuclear Factor-kappaB (NF-?B) is a key regulator of genes involved in M-CSF-induced mononuclear phagocyte survival and this study focused at identifying the mechanism of NF-?B transcriptional activation. Here, we demonstrate that M-CSF stimulated NF-?B transcriptional activity in human monocyte-derived macrophages (MDMs) and the murine macrophage cell line RAW 264.7. The general protein kinase C (PKC) inhibitor Ro-31-8220, the conventional PKC?/? inhibitor Gö-6976, overexpression of dominant negative PKC? constructs and PKC? siRNA reduced NF-?B activity in response to M-CSF. Interestingly, Ro-31-8220 reduced Ser276 phosphorylation of NF-?Bp65 leading to decreased M-CSF-induced monocyte survival. In this report, we identify conventional PKCs, including PKC? as important upstream kinases for M-CSF-induced NF-?B transcriptional activation, NF-?B-regulated gene expression, NF-?B p65 Ser276 phosphorylation, and macrophage survival. Lastly, we find that NF-?B p65 Ser276 plays an important role in basal and M-CSF-stimulated NF-?B activation in human mononuclear phagocytes.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC3245220 | biostudies-other | 2011

REPOSITORIES: biostudies-other