Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, GA.
Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, GA.
Int Forum Allergy Rhinol. 2018 Oct;8(10):1184-1189. doi: 10.1002/alr.22163. Epub 2018 Jun 13.
The endocannabinoid system represents a highly conserved, innate signaling network with direct and indirect control of eicosanoid-mediated inflammation. Activation of the type 2 cannabinoid receptor (CB2R) leads to decreased type 2 inflammation and reduced production of arachidonic acid (AA). Given that altered AA metabolism is associated with aspirin-exacerbated respiratory disease (AERD), we hypothesized that expression of the CB2R gene CNR2 is increased in AERD.
Nasal polyps from consecutive patients undergoing endoscopic sinus surgery for AERD or allergic fungal rhinosinusitis (AFRS) were prospectively evaluated. Control sphenoid mucosa was collected from patients undergoing endoscopic skull base procedures. Expression and localization of endocannabinoid receptors were evaluated by quantitative reverse transcript-polymerase chain reaction (qRT-PCR) and immunohistochemistry. A 2-group unpaired t test with unequal variances was used to evaluate group differences.
Thirteen subjects were included in this pilot study, including 5 controls, 5 AFRS patients, and 3 AERD patients. Upregulated expression of CNR2 was detected in subjects with AERD vs both AFRS (p = 0.049) and controls (p = 0.047), with a mean increase of 5.2-fold. No significant differences in expression of the CB1R gene CNR1 were detected between control and AFRS groups. Immunohistochemistry predominantly localized CB1R and CB2R expression to the surface epithelium in all subjects.
The endocannabinoid system is an emerging immunomodulatory network that may be involved in AERD. This is the first study of CB2R in sinonasal disease, showing significantly increased transcription in nasal polyps from subjects with AERD. Additional study is warranted to further evaluate the contribution and therapeutic potential of this novel finding in chronic rhinosinusitis.
内源性大麻素系统代表着一个高度保守的先天信号网络，可直接和间接控制类二十烷酸介导的炎症。2 型大麻素受体（CB2R）的激活可导致 2 型炎症减少和花生四烯酸（AA）产生减少。鉴于 AA 代谢改变与阿司匹林加重的呼吸道疾病（AERD）有关，我们假设 AERD 中 CB2R 基因 CNR2 的表达增加。
前瞻性评估连续因 AERD 或变应性真菌性鼻鼻窦炎（AFRS）而行内镜鼻窦手术的患者的鼻息肉。从接受内镜颅底手术的患者中采集对照性蝶窦黏膜。通过定量逆转录聚合酶链反应（qRT-PCR）和免疫组织化学评估内源性大麻素受体的表达和定位。采用两组不等方差的独立样本 t 检验评估组间差异。
本研究纳入了 13 名患者，包括 5 名对照者、5 名 AFRS 患者和 3 名 AERD 患者。与 AFRS 患者（p = 0.049）和对照组（p = 0.047）相比，AERD 患者中 CNR2 的表达上调，平均上调 5.2 倍。在对照组和 AFRS 组之间，CNR1 基因 CB1R 的表达无显著差异。免疫组织化学主要将 CB1R 和 CB2R 表达定位于所有患者的表面上皮。
内源性大麻素系统是一个新兴的免疫调节网络，可能与 AERD 有关。这是关于鼻内疾病中 CB2R 的第一项研究，显示 AERD 患者的鼻息肉中转录明显增加。需要进一步研究以进一步评估这一新型发现对慢性鼻-鼻窦炎的贡献和治疗潜力。
