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

• Published in: Allergy (Copenhagen) 2024-11, Vol.79 (11), p.3095-3107
• Main Authors: Khalmuratova, Roza, Ryu, Jae‐Sung, Hwang, Ji Hyeon, Kim, Yi Sook, Lim, Suha, Mo, Ji‐Hun, Kim, Jong‐Yeup, Shin, Hyun‐Woo
• Format: Article
• Language: English
• Subjects: Adult; Allergic diseases; Animals; Biopsy; Chronic Disease; Cytokines - metabolism; Disease Models, Animal; Epithelial cells; Epithelium; Female; Humans; Hypoxia; Immune response; Immunoblotting; Immunofluorescence; Male; Mice; Middle Aged; Nasal Mucosa - metabolism; Nasal Mucosa - pathology; nasal polyps; Nasal Polyps - metabolism; Neuropilin; Neuropilin-1 - antagonists & inhibitors; Neuropilin-1 - metabolism; neuropilin‐1; Nitric-oxide synthase; Polyposis; Polyps; Prostaglandin E2; Prostaglandin endoperoxide synthase; Respiratory tract diseases; Rhinitis - metabolism; Rhinosinusitis; Sinusitis - metabolism; Therapeutic targets; upper airway inflammatory diseases; Vascular endothelial growth factor
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.16285

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. This study aims to elucidate the role of NRP1 in CRSwNP. Expression of NRP1 is increased in the epithelium in patients with CRSwNP. Hypoxia upregulates NRP1 expression in human nasal epithelial cells. The inhibition of NRP1 attenuates secretion of IL‐1β, IL‐6, IL‐8, and IL‐33. Abbreviations: CRSsNP, chronic rhinosinusitis without nasal polyps; CRSwNP, chronic rhinosinusitis with nasal polyps; HIF‐1α, hypoxia‐inducible factor 1 alpha; HNECs, human nasal epithelial cells; IHC, immunohistochemistry; IL, interleukin; NP, nasal polyp; NRP1, neuropilin 1