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Ghavami, Saeid; Rashedi, Iran; Dattilo, Brian M.; Eshraghi, Mehdi; Chazin, Walter J.; Hashemi, Mohammad; Wesselborg, Sebastian; Kerkhoff, Claus; Los, Marek
Journal of leukocyte biology, June 2008, Letnik: 83, Številka: 6Journal Article
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‐κB 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‐κB activation. RAGE small interfering RNA pretreatment abrogated the S100A8/A9‐induced NF‐κB activation. Our data indicate that S100A8/A9‐promoted cell growth occurs through RAGE signaling and activation of NF‐κB.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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