ArticleScientific reports2015
TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- A UK Biobank Study on Genetic Variants in Pattern-Recognition Receptor (PRR) Signaling Indicates Self-Perpetuatin Inflammation of Cholesteatoma.Journal of personalized medicine · 2026Article
- Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.Current medicinal chemistry · 2026Review
- Diagnostic Pitfalls of External Auditory Canal Cholesteatoma: Insights From a Case Report.Cureus · 2025Article
- Host-Microbe Interactions in Healthy and CSOM-Affected Middle Ears.Microorganisms · 2025Article
- Role of TLR4 activation and signaling in bone remodeling, and afferent sprouting in serum transfer arthritis.Arthritis research & therapy · 2024Article
- PTHrP participates in the bone destruction of middle ear cholesteatoma via promoting macrophage differentiation into osteoclasts induced by RANKL.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Sensorineural hearing loss and cognitive impairment: three hypotheses.Frontiers in aging neuroscience · 2024Review
- The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.Molecular & cellular proteomics : MCP · 2023Article
- Hearing rehabilitation and microbial shift after middle ear surgery with Vibrant Soundbridge in patients with chronic otitis media.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023Article
- Micro RNAs and Circular RNAs in Different Forms of Otitis Media.International journal of molecular sciences · 2023Review
- The Role of Extracellular Vesicles in Diseases of the Ear, Nose, and Throat.Medical sciences (Basel, Switzerland) · 2022Review
- Review of potential medical treatments for middle ear cholesteatoma.Cell communication and signaling : CCS · 2022Review
- Endotyping of Cholesteatoma: Which Molecular Biomarkers? A Systematic Review.Journal of personalized medicine · 2022Review
- The Relationship between the M1/M2 Macrophage Polarization and the Degree of Ossicular Erosion in Human Acquired Cholesteatoma: An Immunohistochemical Study.Journal of clinical medicine · 2022Article
- Cytokine secretion and pyroptosis of cholesteatoma keratinocytes mediated by AIM2 inflammasomes in response to cytoplasmic DNA.Molecular medicine reports · 2021Article
- Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism.Cell communication and signaling : CCS · 2021Article
- Bone turnover in chronic otitis media with bone destruction.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2020Article
- Stem Cell-Induced Inflammation in Cholesteatoma is Inhibited by the TLR4 Antagonist LPS-RS.Cells · 2020Article
- Extensive qPCR analysis reveals altered gene expression in middle ear mucosa from cholesteatoma patients.PloS one · 2020Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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