Activation of the TLR2-mediated downstream signaling pathways NF-kappa B and MAPK is responsible for B7-H3-augmented inflammatory response during S. pneumoniae infection

作者：Chen, Xuqin; Meng, Xiangying; Foley, Niamh M.; Shi, Xiaoyan; Liu, Min; Chai, Yahui; Li, Yiping; Redmond, H. Paul; Wang, Jian; Wang, Jiang Huai^*

来源：Journal of Neuroimmunology, 2017, 310: 82-90.

DOI：10.1016/j.jneuroim.2017.07.002

• B7-H3
• TLR2 signaling
• NF-kappa B pathway
• MAPK pathway
• Cytokines and chemokines
• Microglial cells

It has been reported that B7-H3, a costimulatory protein, participates in the development and progression of experimental pneumococcal meningitis by amplifying the TLR2-mediated inflammatory response. This study attempted to clarify the pathway(s) of TLR2 signaling involved in B7-H3-augmented inflammatory response during S. pneumoniae infection. Murine microglial cell line N9 cells and primary murine microglial cells were infected with S. pneumoniae alone or in combination with B7-H3. Although B7-H3 stimulation failed to further enhance S. pneumoniae-upregulated mRNA and protein expression of TLR2, it strongly augmented S. pneumoniae-induced phosphorylation of NF-kappa B p65, MAPK p38, and ERK1/2 in both N9 cells and primary microglial cells. Notably, B7-H3 itself did not activate NF-kappa B p65, MAPK p38, and ERK1/2. Furthermore, deactivation of NF-kappa B p65, MAPK p38, and ERK1/2 with their specific inhibitors significantly attenuated B7-H3-amplified proinflammatory cytokine and chemokine release from S. pneumoniae-infected microglial cells. Importantly, blockage of NF-kappa B p65, MAPK p38, or ERK1/2 in vivo substantially diminished B7-H3-augmented TNF-alpha levels in the brain of S. pneumoniae-infected mice. These results indicate that the activation of both NF-kappa B and MAPKs is predominantly responsible for B7-H3-augmented inflammatory response during S. pneumoniae infection.

• 出版日期2017-9-15
• 单位苏州大学