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YOUAH Home » science news » Proinflammatory Proteins S100A8/S100A9 Activate NK Cells via Interaction with RAGE TUMOR IMMUNOLOGY]
Friday, 20 Oct 2017

Proinflammatory Proteins S100A8/S100A9 Activate NK Cells via Interaction with RAGE TUMOR IMMUNOLOGY]

S100A8/A9, a proinflammatory protein, is upregulated in inflammatory diseases, and also has a tumor-promoting activity by the recruitment of myeloid cells and tumor cell invasion. However, whether the expression of S100A8/A9 in tumors predicts a good or poor prognosis is controversial in the clinical setting. In this study, to clarify the in vivo role of S100A8/A9 in the tumor microenvironment, we s.c. inoculated Pan02 cells stably expressing S100A8 and S100A9 proteins (Pan02-S100A8/A9) in syngeneic C57BL/6 mice. Unexpectedly, after small tumor nodules were once established, they rapidly disappeared. Flow cytometry showed that the number of NK cells in the tumors was increased, and an administration of anti-asialoGM1 Ab for NK cell depletion promoted the growth of Pan02-S100A8/A9 s.c. tumors. Although the S100A8/A9 proteins alone did not change the IFN- expression of NK cells in vitro, a coculture with Pan02 cells, which express Rae-1, induced IFN- production, and Pan02-S100A8/A9 cells further increased the number of IFN-+ NK cells, suggesting that S100A8/A9 enhanced the NK group 2D ligand-mediated intracellular activation pathway in NK cells. We then examined whether NK cell activation by S100A8/A9 was via their binding to receptor of advanced glycation end product (RAGE) by using the inhibitors. RAGE antagonistic peptide and anti-RAGE Ab inhibited the IFN- production of NK cells induced by S100A8/A9 proteins, and an administration of FPS-ZM1, a RAGE inhibitor, significantly enhanced the in vivo growth of Pan02-S100A8/A9 tumors. We thus found a novel activation mechanism of NK cells via S100A8/A9–RAGE signaling, which may open a novel perspective on the in vivo interaction between inflammation and innate immunity.

Read more: Proinflammatory Proteins S100A8/S100A9 Activate NK Cells via Interaction with RAGE TUMOR IMMUNOLOGY]

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