Tumour necrosis factor alpha and interleukin-5 inhibit olfactory regeneration via apoptosis of olfactory sphere cells in mice models of allergic rhinitis
Dong-Kyu Kim
Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital and Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, South Korea
Search for more papers by this authorSeung Ah Choi
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorKyoung Mi Eun
Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorSeung-Ki Kim
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Dae Woo Kim
Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea
Correspondence
Dae Woo Kim, Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, 425 Shindaebang 2-dong, Dongjak-Gu, Seoul 07061, South Korea.
Email: [email protected]
and
Ji Hoon Phi, Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, 101 Daehakro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Ji Hoon Phi
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Correspondence
Dae Woo Kim, Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, 425 Shindaebang 2-dong, Dongjak-Gu, Seoul 07061, South Korea.
Email: [email protected]
and
Ji Hoon Phi, Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, 101 Daehakro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
Search for more papers by this authorDong-Kyu Kim
Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital and Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, South Korea
Search for more papers by this authorSeung Ah Choi
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorKyoung Mi Eun
Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorSeung-Ki Kim
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Dae Woo Kim
Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea
Correspondence
Dae Woo Kim, Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, 425 Shindaebang 2-dong, Dongjak-Gu, Seoul 07061, South Korea.
Email: [email protected]
and
Ji Hoon Phi, Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, 101 Daehakro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Ji Hoon Phi
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, South Korea
Correspondence
Dae Woo Kim, Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, 425 Shindaebang 2-dong, Dongjak-Gu, Seoul 07061, South Korea.
Email: [email protected]
and
Ji Hoon Phi, Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, 101 Daehakro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
Search for more papers by this authorAbstract
Background
Olfactory dysfunction is frequently experienced by patients with allergic rhinitis. It is thought to result from structural and functional changes occurring in the olfactory mucosa caused by inflammation. However, the current understanding of the pathophysiology of olfactory dysfunction in allergic rhinitis remains unclear.
Objective
To investigate the mechanism by which the olfactory neural cells are damaged in allergic rhinitis.
Methods
Olfactory sphere cells (OSCs) were established after dissociation and serial cultures of cells from the mouse olfactory mucosa. Viability and proliferation of OSCs were compared between control and allergic rhinitis mice models, and olfactory stem cell markers were analysed in vivo. To elucidate which cytokines have an inhibitory effect on OSCs, viability and apoptotic markers of OSCs were investigated.
Results
Olfactory sphere cells were successfully isolated from the olfactory mucosa of mice, and these cells expressed markers of neural stem cells. To investigate the neural differentiation, we performed the immunocytochemical staining and found significantly elevated expressions of Tuji1, GFAP and O4 on OSCs. On the comparison of the characteristics of OSCs between control and allergic rhinitis model, we detected significantly fewer neurospheres, reduced clonogenic capacity and decreased expression of olfactory neural stem cell markers in allergic rhinitis model. When OSCs were treated with several major allergic cytokines were treated on OSCs, only TNF-α showed an inhibitory effect on OSCs. Interestingly, IL-5 had an inhibitory effect on the viability of OSCs in combination with TNF-α, whereas IL-5 alone does not have an effect. Moreover, TNF-α combined with IL-5 significantly increased the apoptotic expression, compared with TNF-α or IL-5 alone. Additionally, allergic rhinitis mice models showed the increased apoptotic expression.
Conclusion and Clinical Relevance
Allergic rhinitis mice models showed lower expression of OSCs, and TNF-α combined with IL-5 had an apoptotic effect on OSCs. Therefore, these cytokines may be therapeutic targets for olfactory dysfunction in patients with allergic rhinitis.
CONFLICT OF INTEREST
The authors declare that they have no relevant conflicts of interest.
Supporting Information
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| cea13401-sup-0004-TableS1.docxWord document, 14.2 KB |
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