NRP1 antagonism as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis.

Autor: Khalmuratova R; Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.; Ischemic Hypoxia Disease Institute, Seoul National University Medical Research Center, Seoul, Korea., Ryu JS; Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Korea.; Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Korea., Hwang JH; Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Korea.; Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Korea., Kim YS; Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.; Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea., Lim S; Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea., Mo JH; Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Korea.; Beckman Laser Institute Korea, Dankook University College of Medicine, Cheonan, Korea., Kim JY; Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Korea.; Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Korea., Shin HW; Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.; Ischemic Hypoxia Disease Institute, Seoul National University Medical Research Center, Seoul, Korea.; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.; Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2024 Nov; Vol. 79 (11), pp. 3095-3107. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1111/all.16285
Abstrakt: Background: Neuropilin-1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP).
Methods: Sinonasal biopsy specimens were immunohistochemically stained to investigate NRP1 expression. Double immunofluorescence, immunoblotting, and real-time polymerase chain reaction were performed to evaluate NRP1 in primary human nasal epithelial cells (hNECs). An NRP1 inhibitor was administered to a murine nasal polyp (NP) model.
Results: NRP1 was highly expressed in the epithelium in patients with CRSwNP compared to nasal tissue from controls and CRS without NP patients. NRP1 and vascular endothelial growth factor were upregulated in hNECs under hypoxia. Treatment with NRP1 inhibitor (EG00229) reduced the secretion of interleukin (IL)-1β, IL-6, IL-8, and IL-33 cytokines, as well as inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 in hNECs. We found that NRP1 was highly expressed in the airway epithelium in the murine NP model. The group treated with the NRP1 inhibitor had significantly fewer nasal polypoid lesions and reduced accumulations of immune cells.
Conclusions: These findings reveal that NRP1 is upregulated in CRS and NP epithelium, and the inhibition of NRP1 may lead to a reduction in NP growth and immune cell infiltration. Our results suggest that NRP1 inhibition could be a novel possibility for treating nasal polyposis.
(© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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