Fig. 8

Scheme of roles of PDI in the integration of TLR4- and P2X7R-mediated signaling pathways during inflammation. LPS-induced TLR4 activation led to NF-κB activation by S-nitrosylation and phosphorylation of p65 subunit, which upregulated iNOS and PDI expression in microglia. S-nitrosylation of PDI induced by iNOS further augmented NF-κB activation by a direct interaction as well as the enhanced surface P2X7R expression, independent of S-nitrosylation of p65.