Role of the type I tumor necrosis factor receptor in inflammation-associated olfactory dysfunction.
To understand mechanisms of human olfactory dysfunction in chronic rhinosinusitis, an inducible olfactory inflammation (IOI) model has been utilized to chronically express inflammatory cytokines locally, resulting in neuronal loss, diminished odorant responses, and repressed olfactory regeneration. Knockout of the minor tumor necrosis factor α receptor 2 (TNFR2) was previously shown to partially rescue these olfactory changes. The purpose of current study was to investigate the role of the major TNF receptor, TNFR1, in chronic olfactory inflammation.



Two experimental groups of mice were studied: TNFR1 knockout in IOI background and TNFR1 knockout with allergen-induced inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining.



TNF-α was dramatically induced in IOI-TNFR1 knockout mice, but the olfactory epithelium did not show inflammation. EOG responses were normal after either 2 or 8 weeks of TNF-α expression. Ovalbumin-sensitized TNFR1 knockout mice developed markedly diminished eosinophilic inflammatory infiltration.



Genetic deletion of TNFR1 completely blocks TNF-α-induced inflammation and reduces allergen-induced inflammation. Preserved EOG responses suggest a TNFR1-dependent mechanism of TNF-α-induced olfactory neuron dysfunction.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.|Department of Otolaryngology, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, Brazil.
Davi
D
Sousa Garcia
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Mengfei
M
Chen
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Amy K
AK
Smith
Department of Otolaryngology, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, Brazil.
Paulo Roberto
PR
Lazarini
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Andrew P
AP
Lane
D000485:Allergens; D000534:Alum Compounds; D000818:Animals; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008297:Male; D018345:Mice, Knockout; D017817:Nasal Lavage Fluid / Q000276:immunology; D009474:Neurons / Q000502:physiology; D000857:Olfaction Disorders / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D009831:Olfactory Mucosa / Q000473:pathology; D010047:Ovalbumin; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000485:Allergens; D000534:Alum Compounds; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; C041524:aluminum sulfate; D010047:Ovalbumin
TNF-alpha; TNFR1; eosinophils; inflammation; olfactory epithelium; transgenic mice
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