Larsson Olivia, Sunnergren Ola, Bachert Claus, Kumlien Georén Susanna, Cardell Lars Olaf
Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Otorhinolaryngology, Ryhov County Hospital, Jönköping, Sweden.
Clin Transl Allergy. 2021 Mar;11(1):e12009. doi: 10.1002/clt2.12009.
Substance P (SP) and toll-like receptors (TLRs) contribute to airway disease, particularly during viral infection. We recently demonstrated that SP can act as an initial response to viral stimuli in the upper airway by upregulating TLRs in the nasal epithelia (the SP-TLR axis). Patients with allergic rhinitis (AR) suffer from prolonged airway infections. The aim of the present study was to examine if patients with AR exhibit a disturbance in the SP-TLR axis.
Human nasal biopsies and human nasal epithelial cells (HNEC) from healthy volunteers and patients with AR were cultured in the presence of SP. Epithelial expression of TLR4, neutral endopeptidase (NEP) and neurokinin 1 (NK1) were evaluated with flow cytometry and/or quantitative polymerase chain reaction after 30 min to 24 h. The effect of SP on nasal lipopolysaccharide-induced interleukin-8 (IL-8) release was investigated.
SP stimulation of tissue from healthy volunteers resulted in a transient increase of the TLR4 expression, whereas stimulation of AR patient-derived material led to a delayed and prolonged upregulation of TLR4. NEP expression in HNEC was lower in AR than healthy controls whereas NK1 receptor expression was increased. SP pretreatment increased TLR4-dependent IL-8 expression in healthy controls, but not in AR.
SP-induced regulation of TLR4 in the human nasal mucosa is disturbed in AR. An altered SP-mediated innate immune response may contribute to the dysfunctional and often prolonged responses to infection in AR.
P物质（SP）和Toll样受体（TLR）与气道疾病有关，尤其是在病毒感染期间。我们最近证明，SP可通过上调鼻上皮中的TLR（SP-TLR轴），对上呼吸道中的病毒刺激作出初始反应。过敏性鼻炎（AR）患者易患持续性气道感染。本研究的目的是检验AR患者是否存在SP-TLR轴紊乱。
将来自健康志愿者和AR患者的人鼻活检组织及人鼻上皮细胞（HNEC）在SP存在的情况下进行培养。在30分钟至24小时后，通过流式细胞术和/或定量聚合酶链反应评估TLR4、中性内肽酶（NEP）和神经激肽1（NK1）的上皮表达。研究了SP对鼻内脂多糖诱导的白细胞介素-8（IL-8）释放的影响。
SP刺激健康志愿者的组织导致TLR4表达短暂增加，而刺激AR患者来源的材料则导致TLR4延迟且持续上调。AR患者HNEC中的NEP表达低于健康对照组，而NK1受体表达增加。SP预处理增加了健康对照组中TLR4依赖性IL-8的表达，但在AR患者中未增加。
AR患者鼻黏膜中SP诱导的TLR4调节受到干扰。SP介导的先天性免疫反应改变可能导致AR患者对感染的功能失调且通常持续时间较长的反应。
