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BackgroundFractalkine is widely expressed throughout the brain and spinal cord, where it can exert effects on pain enhancement and hyperalgesia by activating microglia through CX3C chemokine receptor 1 (CX3CR1), which triggers the release of several pro-inflammatory cytokines in the spinal cord. Fractalkine has also been shown to increase cytosolic calcium ([Ca2+]i) in microglia.Material/MethodsBased on the characteristics of CX3CR1, a G protein-coupled receptor, we explored the role of inositol 1,4,5-trisphosphate (IP3) signaling in fractalkine-induced inflammatory response in BV-2 cells in vitro. The effect and the underlying mechanism induced by fractalkine in the brain were observed using a mouse model with intracerebroventricular (i.c.v.) injection of exogenous fractalkine.Results[Ca2+]i was significantly increased and IL-1β and TNF-α levels were higher in the fractalkine-treated cell groups than in the farctalkine+ 2-APB groups. We found that i.c.v. injection of fractalkine significantly increased p-p38MAPK, IL-1β, and TNF-α expression in the brain, while i.c.v. injection of a fractalkine-neutralizing antibody (anti-CX3CR1), trisphosphate receptor (IP3R) antagonist (2-APB), or p38MAPK inhibitor (SB203580) prior to fractalkine addition yielded an effective and reliable anti-allodynia effect, following the reduction of p-p38MAPK, IL-1β, and TNF-α expression.ConclusionsOur results suggest that fractalkine leads to hyperalgesia, and the underlying mechanism may be associated with IP3/p38MAPK-mediated calcium signaling and its phlogogenic properties.

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Background: The aim of this study was to confirm the role of nuclear pore membrane protein 121(POM121) in oral squamous cell carcinoma and to explore the underlying mechanism.Methods: POM121mRNA and protein expressions were evaluated in OSCC tissues and normal oral tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The relationship between POM121 expression and clinical characteristics was analyzed. Bioinformatics analysis was performed to explore the possible mechanisms how POM121 affected OSCC.Results: We confirmed that POM121 mRNA expression in OSCC tissues was significantly higher than that in non-tumorous tissues, as was POM121 protein expression. POM121 expression was associated with distant metastasis and TNM stage. Multivariate analysis confirmed POM121 expression as an independent prognostic factor for OSCC patients. OSCC patients with high POM121 expression had a worse overall survival (OS) compared with patients with low POM121 expression. Bioinformatics analysis indicated POM121 may regulate OSCC through hedgehog and /or p53 signaling pathway.Conclusion: Targeting of POM121 expression levels could provide new diagnostic and therapeutic strategies for OSCC patients.