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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 / Copyright

    Affiliations: Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 31-38
    |
    Published online on: May 12, 2017
       https://doi.org/10.3892/ijmm.2017.2987
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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