title: Activation of NF-κB signaling pathway in HSV-1-induced mouse facial palsy: Possible relation to therapeutic effect of glucocorticoids.
abstract: 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-κB) and its consequent effect on two key inflammatory factors, i.e., tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2), as well as the effect of glucocorticoids (GCs) in this work. I-kappa B (IκB)-α phosphorylation and NF-κB nuclear translocation were measured by western blotting, and NF-κB/DNA binding activity was assessed by electrophoretic mobility shift assay (EMSA). Results showed the IκB-α phosphorylation and degradation as well as NF-κB activation in a time-dependent manner. The expression of TNF-α 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-α and COX-2 were rapidly induced in HSV-1-infected paralyzed mice. Conversely, the activation of NF-κB and up-regulation of TNF-α and COX-2 were blocked by pretreatment with NF-κB 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-κB via inhibiting IκB-α degradation. Meanwhile, TNF-α production and COX-2 expression were significantly reduced by GCs. In conclusion, HSV-1 inoculation induced the activation of NF-κB, expression and secretion of TNF-α and COX-2 in the facial paralyzed mice, while, glucocorticoid effectively down-regulated TNF-α and COX-2 expression in HSV-1-induced paralyzed mice.
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China; Institute of Eye and ENT, Provincial Hospital Affiliated to Shandong University, Jinan, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China; Institute of Eye and ENT, Provincial Hospital Affiliated to Shandong University, Jinan, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Shandong Provincial Key Laboratory of Otology, Jinan, PR China; Institute of Eye and ENT, Provincial Hospital Affiliated to Shandong University, Jinan, PR China. Electronic address: lijianfeng@hotmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China; Institute of Eye and ENT, Provincial Hospital Affiliated to Shandong University, Jinan, PR China. Electronic address: wang.hb7585@hotmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005158:Facial Paralysis / Q000188:drug therapy* / Q000503:physiopathology*; D005938:Glucocorticoids / Q000008:administration & dosage*; D018259:Herpesvirus 1, Human; D006727:Hormone Antagonists / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000378:metabolism; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D006727:Hormone Antagonists; D016328:NF-kappa B; D011759:Pyrrolidines; D011965:Receptors, Glucocorticoid; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D015735:Mifepristone; D008776:Methylprednisolone Hemisuccinate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase
keywords: cyclooxygenase-2; facial palsy; glucocorticoid; herpes simplex virus type 1; nuclear factor-kappa B; tumor necrosis factor-α