Open Access

Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells

  • Authors:
    • Li Ma
    • Peng Sun
    • Jian-Cheng Zhang
    • Qing Zhang
    • Shang-Long Yao
  • View Affiliations

  • Published online on: May 12, 2017     https://doi.org/10.3892/ijmm.2017.2987
  • Pages: 31-38
  • Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

S100A8/A9, a heterodimer of the two calcium-binding proteins S100A8 and S100A9, has emerged as an important proinflammatory mediator in acute and chronic inflammation. However, whether S100A8/A9 is implicated in microglial‑induced neuroinflammatory response remains unclear. Here, we found that S100A8/A9 significantly increased the secretion of proinflammatory cytokines inclu­ding tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured BV-2 microglial cells. Inhibition of the Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end-products (RAGE) with C225 and a RAGE-blocking antibody, respectively significantly reduced the secretion of TNF-α and IL-6 from S100A8/A9-stimulated BV-2 microglial cells. Furthermore, S100A8/A9 markedly enhanced the nuclear translocation of NF-κB p65 and the DNA-binding activities of NF-κB in BV-2 microglial cells, and suppression of ERK and JNK/MAPK signaling pathways by PD98059 or SP600125 significantly inhibited NF-κB activity and the release of TNF-α and IL-6 in the S100A8/A9-treated BV-2 microglial cells. Our data also showed that inhibition of NF-κB with pyrrolidine dithiocarbamate (PDTC) significantly reduced the secretion of TNF-α and IL-6 from BV-2 microglial cells treated with S100A8/A9. Taken together, our data suggest that S100A8/A9 acts directly on BV-2 microglial cells via binding to TLR4 and RAGE on the membrane and then stimulates the secretion of proinflammatory cytokines through ERK and JNK-mediated NF-κB activity in BV-2 microglial cells. Targeting S100A8/A9 may provide a novel therapeutic strategy in microglial-induced neuroinflammatory diseases.
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July-2017
Volume 40 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Ma L, Sun P, Zhang J, Zhang Q and Yao S: Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells. Int J Mol Med 40: 31-38, 2017.
APA
Ma, L., Sun, P., Zhang, J., Zhang, Q., & Yao, S. (2017). Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells. International Journal of Molecular Medicine, 40, 31-38. https://doi.org/10.3892/ijmm.2017.2987
MLA
Ma, L., Sun, P., Zhang, J., Zhang, Q., Yao, S."Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells". International Journal of Molecular Medicine 40.1 (2017): 31-38.
Chicago
Ma, L., Sun, P., Zhang, J., Zhang, Q., Yao, S."Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells". International Journal of Molecular Medicine 40, no. 1 (2017): 31-38. https://doi.org/10.3892/ijmm.2017.2987