DEAD-box helicase 54 regulates microglial inflammatory response in rats with chronic constriction injuries through NF-κB/NLRP3 signaling axis

Objective Neuropathic pain (NP) is caused by damage to or disease of the somatosensory nervous system, but its mechanism is still not fully understood. In this study, DEAD-box helicase 54 (DDX54) was targeted, and its regulatory role was explored in a chronic constriction injury (CCI) rat model. Materials and methods Microglia and HMC3 cells were stimulated with LPS. The interaction between DDX54 and the myeloid differentiation factor-88 adapter protein (MyD88) was verified. CCI of sciatic nerve model in rats was established. Behavioral testing was performed before and after the CCI. Results The expressions of IL-1β, TNFα and IL-6 were up-regulated, and those of DDX54, MyD88, NF-κB and NLRP3 were up-regulated in microglia and HMC3 cells after LPS induction. DDX54 knockdown in microglia and HMC3 cells inhibited IL-1β, TNFα and IL-6 expressions, and down-regulated the protein levels of MyD88, p-p65 and NLRP3. DDX54 overexpression promoted the stability of MyD88 mRNA. DDX54 binds to the MYD88-3'UTR region. DDX54 interference in rats could alleviate the decrease of PWMT and PWTL induced by CCI, inhibit Iba1 expression and reduce inflammatory factors as well as MyD88 and NF-κB expressions. Conclusion DDX54 promotes the activation of NF-κB/NLRP3 signaling by regulating MyD88 mRNA stability, thereby affecting inflammatory response and NP progression in CCI rats.

DDX54; MYD88; NF-κB/NLRP3; microglial inflammatory response; neuropathic pain.