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Mitogen‐activated protein kinase pathway mediates DBP–maf‐induced apoptosis in RAW 264.7 macrophages
Author(s) -
Gumireddy Kiranmai,
Reddy C. Damodar,
Swamy Narasimha
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10615
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , apoptosis , microbiology and biotechnology , kinase , signal transduction , protein kinase a , inflammation , chemistry , phosphorylation , biology , biochemistry , immunology
Abstract Vitamin D‐binding protein–macrophage‐activating factor (DBP–maf) is derived from serum vitamin D binding protein (DBP) by selective deglycosylation during inflammation. In the present study, we investigated the effect of DBP–maf on RAW 264.7 macrophages and the underlying intracellular signal transduction pathways. DBP–maf increased proapoptotic caspase‐3, ‐8, and ‐9 activities and induced apoptosis in RAW 264.7 cells. However, DBP, the precursor to DBP–maf did not induce apoptosis in these cells. Cell cycle analysis of DBP–maf‐treated RAW 264.7 cells revealed growth arrest with accumulation of cells in sub‐G 0 /G 1 phase. We also investigated the role of mitogen‐activated protein kinase (MAPK) pathways in the DBP–maf‐induced apoptosis of RAW264.7 cells. DBP–maf increased the phosphorylation of p38 and JNK1/2, while it decreased the ERK1/2 phosphorylation. Treatment with the p38 MAPK inhibitor, SB202190, attenuated DBP–maf‐induced apoptosis. PD98059, a MEK specific inhibitor, did not show a significant inhibition of apoptosis induced by DBP–maf. Taken together, these results suggest that the p38 MAPK pathway plays a crucial role in DBP–maf‐mediated apoptosis of macrophages. Our studies indicate that, during inflammation DBP–maf may function positively by causing death of the macrophages when activated macrophages are no longer needed at the site of inflammation. In summary, we report for the first time that DBP–maf induces apoptosis in macrophages via p38 and JNK1/2 pathway. J. Cell. Biochem. 90: 87–96, 2003. © 2003 Wiley‐Liss, Inc.