Xiaolin Zhang1, Tihua Zheng2, Lu Sang2, Luke Apisa3, Hongchun Zhao4, Fenghua Fu5, Qingzhu Wang2, Yanfei Wang6, Qingyin Zheng7. 1. 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. 2. Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai 264003, Shandong, PR China. 3. Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA. 4. Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, Shandong, PR China. 5. Department of Pharmacology, School of Pharmacy, Yantai University, Yantai 264003, Shandong, PR China. 6. 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. 7. 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.
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.
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.
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