期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 83, 期 6, 页码 1484-1492出版社
WILEY
DOI: 10.1189/jlb.0607397
关键词
NF-kappa B; proliferation; MRP8; MRP14; endokines; S100/calgranulins; cytotoxic peptides
资金
- NIGMS NIH HHS [T32 GM008320-15, T32 GM008320, R01 GM062112-07, R01 GM 62112, T32 GM008320-14, T32 GM 08320, R01 GM062112-08, R01 GM062112] Funding Source: Medline
The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity against various cells, especially tumor cells. Here, we present evidence that S100A8/A9 also has cell growth-promoting activity at low concentrations. Receptor of advanced glycation end product (RAGE) gene silencing and cotreatment with a RAGE-specific blocking antibody revealed that this activity was mediated via RAGE ligation. To investigate the signaling pathways, MAPK phosphorylation and NF-kappa B activation were characterized in S100A8/A9-treated cells. S100A8/A9 caused a significant increase in p38 MAPK and p44/42 kinase phosphorylation, and the status of stress-activated protein kinase/JNK phosphorylation remained unchanged. Treatment of cells with S100A8/ A9 also enhanced NF-kappa B activation. RAGE small interfering RNA pretreatment abrogated the S100A8/ A9-induced NF-kappa B activation. Our data indicate that S100A8/A9-promoted cell growth occurs through RAGE signaling and activation of NF-kappa B.
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