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: Xiaolin Zhang, Tihua Zheng, Lu Sang, Luke Apisa, Hongchun Zhao, Fenghua Fu, Qingzhu Wang, Yanfei Wang, Qingyin Zheng
• Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases (Infect Genet Evol) Vol. 35 Pg. 194-203 (Oct 2015) ISSN: 1567-7257 [Electronic] Netherlands
• PMID: 26296608 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Peptidoglycan
• Saponins
• Tlr2 protein, mouse
• Toll-Like Receptor 2
• Triterpenes
• sodium aescinate

Topics

• Administration, Intravenous
• Animals
• Disease Models, Animal
• Drug Administration Schedule
• Female
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Otitis Media (etiology, genetics, pathology, prevention & control)
• Peptidoglycan (adverse effects)
• Saponins (administration & dosage, pharmacology)
• Signal Transduction (drug effects)
• Toll-Like Receptor 2 (deficiency)
• Triterpenes (administration & dosage, pharmacology)