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Macrophage colony‐stimulating factor promotes monocyte survival through PKC α and NF κ B
Author(s) -
Mo Xiaokui Molly,
Wang Yijie,
Hunter Melissa,
Parinandi Narasimham,
Marsh Clay B
Publication year - 2006
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.20.4.a544-d
Subject(s) - protein kinase c , monocyte , transfection , microbiology and biotechnology , kinase , bryostatin 1 , apoptosis , biology , chemistry , cancer research , cell culture , immunology , biochemistry , genetics
Macrophage colony‐stimulating factor (M‐CSF) is critical in mediating monocyte survival and proliferation. In the absence of M‐CSF, human monocytes undergo spontaneous apoptosis via the activation of caspase‐3. We hypothesized that M‐CSF‐repressed caspase‐3 activation to promote monocyte survival through the activation of protein kinase C (PKC) and NFκB. In both human peripheral blood monocytes (PBM) and NIH 3T3 fibroblasts stably transfected with the human M‐CSF receptor (3T3/fms), we demonstrate that M‐CSF stimulates NFκB transcription activity as measured by secreted alkaline phosphatase (SEAP) reporter system. This activation was repressed by RO‐31‐8220 (PKC inhibitor), and Gö‐6976 (type I PKC inhibitor). Notably, treatment of the PBM with RO‐31‐8220, Gö‐6976, NFκB inhibitor (PDTC), or pIκBα inhibitor (Bay 11‐7082) led to activation of caspase‐3. These observations suggest that PKC modulates NFκB activity and both are required for cell survival. In both systems, we found that PKCαwas activated by M‐CSF. To confirm that PKCα activity was necessary for NFκB activity, we transiently transfected 3T3/fms cells with kinase‐dead PKCα construct and that M‐CSF‐induced NFκB activity was inhibited. Moreover, transfection of monocytes with IκBα super repressor or kinase dead PKCα resulted in the increase of active caspase‐3. These studies demonstrate that NFκB plays a key role in cell survival and its activation induced by M‐CSF is mediated through PKCα.