title: Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2(-/-)) mice for developing drug therapy.
abstract: BACKGROUND
  Toll like receptor 2 (TLR2) signaling can regulate the pathogenesis of otitis media (OM). However, the precise role of TLR2 signaling in OM has not been clarified due to the lack of an optimal animal model. Peptidoglycan-polysaccharide (PGPS) of the bacterial cell wall can induce inflammation by activating the TLR2 signaling. This study aimed at examining the pathogenic characteristics of OM induced by PGPS in Tlr2(-/-) mice, and the potential therapeutic effect of sodium aescinate (SA) in this model.
  
  
  METHODS
  Wild-type (WT) and Tlr2(-/-) mice were inoculated with streptococcal PGPS into their middle ears (MEs) and treated intravenously with vehicle or SA daily beginning at 3days prior to PGPS for 6 consecutive days. The pathologic changes of individual mice were evaluated longitudinally.
  
  
  RESULTS
  In comparison with WT mice, Tlr2(-/-) mice were susceptible to PGPS-induced OM. Tlr2(-/-) mice displayed greater hearing loss, tympanic membrane damage, ME mucosal thickening, longer inflammation state, cilia and goblet cell loss. SA-treatment decreased neutrophil infiltration, modulated TLR2-related gene expression and improved ciliary organization.
  
  
  CONCLUSIONS
  PGPS induced a relatively stable OM in Tlr2(-/-) mice, providing a new model for OM research. Treatment with SA mitigated the pathogenic damage in the ME and may be valuable for intervention of OM.
authors: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai 264003, Shandong, PR China; Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Xiaolin
authors: X
authors: Zhang
authors: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai 264003, Shandong, PR China.
authors: Tihua
authors: T
authors: Zheng
authors: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai 264003, Shandong, PR China.
authors: Lu
authors: L
authors: Sang
authors: Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Luke
authors: L
authors: Apisa
authors: Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, Shandong, PR China.
authors: Hongchun
authors: H
authors: Zhao
authors: Department of Pharmacology, School of Pharmacy, Yantai University, Yantai 264003, Shandong, PR China.
authors: Fenghua
authors: F
authors: Fu
authors: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai 264003, Shandong, PR China.
authors: Qingzhu
authors: Q
authors: Wang
authors: Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, Shandong, PR China. Electronic address: entwyf@163.com.
authors: Yanfei
authors: Y
authors: Wang
authors: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai 264003, Shandong, PR China; Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: qyz@case.edu.
authors: Qingyin
authors: Q
authors: Zheng
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010033:Otitis Media / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D010457:Peptidoglycan / Q000009:adverse effects*; D012503:Saponins / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000172:deficiency*; D014315:Triterpenes / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D010457:Peptidoglycan; D012503:Saponins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014315:Triterpenes; C584713:sodium aescinate
keywords: Mouse models of otitis media; Sodium aescinate; Streptococcal peptidoglycan polysaccharide