ACTIVATION OF NF-kappa B SIGNALING PATHWAY IN HSV-1-INDUCED MOUSE FACIAL PALSY: POSSIBLE RELATION TO THERAPEUTIC EFFECT OF GLUCOCORTICOIDS

作者：Liu W; Fan Z; Han Y; Xu L; Wang M; Zhang D; Mao Y; Li J^*; Wang H

来源：Neuroscience, 2015, 289: 251-261.

DOI：10.1016/j.neuroscience.2014.12.062

• facial palsy
• herpes simplex virus type 1
• nuclear factor-kappa B
• tumor necrosis factor-alpha
• cyclooxygenase-2
• glucocorticoid

It has been documented that infection of herpes simplex virus type 1 (HSV-1) contributes to the initiation of Bell's palsy. However, the exact mechanisms responsible for this disorder have not been fully elucidated to date. A mouse model of facial palsy induced by HSV-1 provides an opportunity to investigate the alteration in activities of nuclear factor-kappa B (NF-kappa B) and its consequent effect on two key inflammatory factors, i.e., tumor necrosis factor (TNF)-alpha and cyclooxygenase-2 (COX-2), as well as the effect of glucocorticoids (GCs) in this work. I-kappa B (I kappa B)-alpha phosphorylation and NF-kappa B nuclear translocation were measured by western blotting, and NF-kappa B/DNA binding activity was assessed by electrophoretic mobility shift assay (EMSA). Results showed the I kappa B-alpha phosphorylation and degradation as well as NF-kappa B activation in a time-dependent manner. The expression of TNF-alpha and COX-2 were determined by real-time polymerase chain reaction (PCR), western blotting and/or enzyme-linked immunosorbent assay (ELISA) respectively. Concomitant with the activation, the expression and secretion of TNF-alpha and COX-2 were rapidly induced in HSV-1-infected paralyzed mice. Conversely, the activation of NF-kappa B and up-regulation of TNF-alpha and COX-2 were blocked by pretreatment with NF-kappa B inhibitor pyrrolidine dithiocarbamate (PDTC) before being inoculated with HSV-1 to mice. In addition, GCs inhibited the nuclear translocation and DNA binding activity of NF-kappa B via inhibiting I kappa B-alpha degradation. Meanwhile, TNF-alpha production and COX-2 expression were significantly reduced by GCs. In conclusion, HSV-1 inoculation induced the activation of NF-kappa B, expression and secretion of TNF-alpha and COX-2 in the facial paralyzed mice, while, glucocorticoid effectively down-regulated TNF-alpha and COX-2 expression in HSV-1-induced paralyzed mice.

• 出版日期2015-3-19
• 单位山东大学