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

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. Microglia and HMC3 cells were stimulated with LPS. The interaction between DDX54 and myeloid differentiation factor-88 adapter protein (MYD88) was verified. A CCI of sciatic nerve model in rats was established. Behavioral testing was performed before and after the CCI. The expressions of IL-1β, TNF-α, and IL-6 were upregulated, and those of DDX54, MYD88, NF-κB, and NOD-like receptor 3 (NLRP3) were upregulated in microglia and HMC3 cells after LPS induction. DDX54 knockdown in microglia and HMC3 cells inhibited IL-1β, TNF-α, and IL-6 expressions and downregulated the protein levels of MYD88, p-NF-κB p65 (p-p65), and NLRP3. DDX54 overexpression promoted the stability of MYD88 mRNA. DDX54 binds to the MYD88-3'-untranslated region (UTR). DDX54 interference in rats could alleviate the decrease of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) induced by CCI, inhibit Iba1 expression, and reduce inflammatory factors as well as MYD88 and NF-κB expressions. DDX54 promotes the activation of NF-κB/NLRP3 signaling by regulating MYD88 mRNA stability, thereby affecting inflammatory response and NP progression in CCI rats. The role of DDX54 protein in LPS-induced microglia and a chronic constriction injury (CCI) rat model was investigated for the first time. DDX54 interference can inhibit microglial activation and reduce the secretion of inflammatory factors. The interaction between DDX54 protein and MYD88 mRNA was explored for the first time. DDX54 promotes NF-κB/NLRP3 signaling activation by regulating MYD88 transcription in a CCI rat model.