TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction
| Autor: | Yi Liu, Yu Si, Sui Jun Chen, Guo Xu, Hao Xiong, Yi Qing Zheng, Huai Li Jiang, Xiang Liu, Yu Bin Chen, Zhuo Hao Li, Zhigang Zhang, Qiu Hong Huang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Adolescent medicine.medical_treatment Osteoclasts Inflammation Cell Count Biology Article Bone and Bones Pathogenesis Young Adult Osteoclast medicine otorhinolaryngologic diseases Evoked Potentials Auditory Brain Stem Animals Humans Cholesteatoma Hearing Loss Aged Demography Multidisciplinary Bacteria Middle Aged medicine.disease Up-Regulation Mice Inbred C57BL Toll-Like Receptor 4 TLR2 medicine.anatomical_structure Cytokine RANKL Immunology biology.protein TLR4 Cytokines Female medicine.symptom Inflammation Mediators |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep16683 |
| Popis: | Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1β. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1β expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis. |
| Databáze: | OpenAIRE |
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