Protein disulfide isomerase integrates toll-like receptor 4 and P2X7 receptor signaling pathways during lipopolysaccharide-induced neuroinflammation.

ABSTRACT: P2X7 receptor (P2X7R) augments lipopolysaccharide (LPS)-toll-like receptor 4 (TLR4)-mediated neuroinflammation. These roles of P2X7R in neuroinflammation are relevant to nitrosative stress through nuclear factor-κB (NF-κB)-inducible nitric oxide synthase (iNOS) pathway, while the underlying mechanisms are largely unknown. In the present study, we investigated whether protein disulfide isomerase (PDI) is involved in the integration of TLR4-P2X7R functions in response to LPS in vivo. The present study showed that LPS elicited NF-κB-mediated PDI upregulation, iNOS induction and S-nitrosylated PDI (SNO-PDI) level, independent of S-nitrosylation of NF-κB p65 subunit, in P2X7R^+/+ mice more than P2X7R^-/- mice. SN50 (an NF-κB inhibitor) effectively diminished LPS-induced PDI

SUBMITTER: Kim JE 

PROVIDER: S-EPMC11885452 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature