PMID- 25595974 OWN - NLM STAT- MEDLINE DCOM- 20151201 LR - 20161125 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 289 DP - 2015 Mar 19 TI - Activation of NF-kappaB signaling pathway in HSV-1-induced mouse facial palsy: Possible relation to therapeutic effect of glucocorticoids. PG - 251-61 LID - S0306-4522(15)00036-6 [pii] LID - 10.1016/j.neuroscience.2014.12.062 [doi] AB - 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-kappaB) 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 (IkappaB)-alpha phosphorylation and NF-kappaB nuclear translocation were measured by western blotting, and NF-kappaB/DNA binding activity was assessed by electrophoretic mobility shift assay (EMSA). Results showed the IkappaB-alpha phosphorylation and degradation as well as NF-kappaB 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-kappaB and up-regulation of TNF-alpha and COX-2 were blocked by pretreatment with NF-kappaB 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-kappaB via inhibiting IkappaB-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-kappaB, 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. CI - Copyright (c) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Liu, W AU - Liu W AD - 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. FAU - Fan, Z AU - Fan Z AD - Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. FAU - Han, Y AU - Han Y AD - Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. FAU - Xu, L AU - Xu L AD - Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. FAU - Wang, M AU - Wang M AD - Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. FAU - Zhang, D AU - Zhang D AD - Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. FAU - Mao, Y AU - Mao Y AD - 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. FAU - Li, J AU - Li J AD - 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. FAU - Wang, H AU - Wang H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150113 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glucocorticoids) RN - 0 (Hormone Antagonists) RN - 0 (NF-kappa B) RN - 0 (Pyrrolidines) RN - 0 (Receptors, Glucocorticoid) RN - 0 (Thiocarbamates) RN - 0 (Tumor Necrosis Factor-alpha) RN - 25769-03-3 (pyrrolidine dithiocarbamic acid) RN - 320T6RNW1F (Mifepristone) RN - 5GMR90S4KN (Methylprednisolone Hemisuccinate) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.10 (Chuk protein, mouse) RN - EC 2.7.11.10 (I-kappa B Kinase) SB - IM MH - Active Transport, Cell Nucleus MH - Animals MH - Anti-Inflammatory Agents/*administration & dosage MH - Brain Stem/drug effects/*physiopathology MH - Cyclooxygenase 2/metabolism MH - Disease Models, Animal MH - Facial Paralysis/*drug therapy/*physiopathology MH - Glucocorticoids/*administration & dosage MH - Herpesvirus 1, Human MH - Hormone Antagonists/pharmacology MH - I-kappa B Kinase/metabolism MH - Male MH - Methylprednisolone Hemisuccinate/administration & dosage MH - Mice, Inbred BALB C MH - Mifepristone/pharmacology MH - NF-kappa B/*metabolism MH - Pyrrolidines/pharmacology MH - Receptors, Glucocorticoid/antagonists & inhibitors/metabolism MH - Signal Transduction/drug effects MH - Thiocarbamates/pharmacology MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - cyclooxygenase-2 OT - facial palsy OT - glucocorticoid OT - herpes simplex virus type 1 OT - nuclear factor-kappa B OT - tumor necrosis factor-alpha EDAT- 2015/01/18 06:00 MHDA- 2015/12/15 06:00 CRDT- 2015/01/18 06:00 PHST- 2014/09/11 00:00 [received] PHST- 2014/12/23 00:00 [revised] PHST- 2014/12/24 00:00 [accepted] PHST- 2015/01/18 06:00 [entrez] PHST- 2015/01/18 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S0306-4522(15)00036-6 [pii] AID - 10.1016/j.neuroscience.2014.12.062 [doi] PST - ppublish SO - Neuroscience. 2015 Mar 19;289:251-61. doi: 10.1016/j.neuroscience.2014.12.062. Epub 2015 Jan 13.