Involvement of galanin and galanin receptor 2 in a mouse model of allergic rhinitis
Involvement of galanin and galanin receptor 2 in a mouse model of allergic rhinitis
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DOI：
10.1016/j.alit.2021.07.012
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发表时间：
2022-01-08
影响因子：
6.8
通讯作者：
Saito, Koichiro
中科院分区：
文献类型：
--
作者：
Kawada, Michitsugu;Yokoi, Hidenori;Saito, Koichiro
背景：变应性鼻炎(AR)是由花粉等变应原引起的过敏反应引起的。甘丙肽(Galanin，GAL)是一种调节炎症过程的神经肽，在中枢和外周神经系统中广泛表达。虽然神经肽与关节炎和化学性回肠炎有关，但它们在AR中的作用仍不清楚。方法：我们建立了AR小鼠模型，并产生对照组、全身敏感组、轻度AR组和重度AR组。我们用逆转录聚合酶链式反应、免疫印迹和免疫组织化学分析检测了每组的GAL和GAL受体(GALR)的mRNA、蛋白水平和定位模式。此外，我们还评价了GALR2拮抗剂M871对重症急性呼吸窘迫小鼠的影响。结果：GAL和Galr2在正常和AR小鼠的鼻黏膜和脑(对照)样本中都有表达。GAL和GALR2在4组鼻黏膜纤毛上皮和粘膜下腺细胞中的表达水平相似，均定位于纤毛上皮和粘膜下腺细胞。与对照组相比，鼻腔注射M871显著降低了重度AR小鼠的揉鼻行为和打喷嚏的发生率(P<；30min分别为0.001)。从机制上，我们假设GALR2在B细胞中表达，而M871的应用减少了组织中IgE的产生和B细胞的数量。结论：GAL信号可能不会随着鼻腔致敏程度的增加而逐渐改变，这一信号过程可能会加剧AR，而不是直接触发AR。GALeGALR2信号可能介导AR的发生，提示其抑制代表了AR的一种新的治疗策略。版权所有(C)2021，日本过敏学会。由爱思唯尔B.V.制作和托管。这是CC By-NC-ND许可证(http://creativecommons.org/licenses/by-nc-nd/4.0/).下的一篇开放获取文章
Background: Allergic rhinitis (AR) is caused by allergic reaction to allergens such as pollen. Galanin (GAL), a neuropeptide that regulates inflammatory processes, is widely expressed in the central and peripheral nervous systems. Although neuropeptides are implicated in arthritis and chemically induced ileitis, their roles in AR remain unclear.Methods: We developed a murine model of AR and generated control, systemic sensitization, mild AR, and severe AR groups. We examined GAL and GAL receptor (GALR) mRNA and protein levels and localization patterns in each group using reverse transcription PCR, western blotting, and immunohistochemical analyses. Additionally, we evaluated the effects of M871, a GALR2 antagonist, on mice with severe AR.Results: Gal and Galr2 are expressed in nasal mucosa and brain (control) samples from control and AR mice. GAL and GALR2 were expressed at similar levels and localized to ciliated epithelial and submucosal gland cells of the nasal mucosa in all four groups. Intranasal M871 administration significantly reduced the incidence of nose rubbing behaviors and sneezing (p < 0.001 in 30 min, respectively) in severe AR mice relative to that in controls. Mechanistically, we postulate that GALR2 is expressed in B cells, and M871 administration reduces IgE production, as well as the number of B cells in tissues.Conclusions: GAL signaling may not change progressively with increasing nasal sensitization, suggesting that this signaling process exacerbates, rather than directly trigger, AR. GALeGALR2 signaling likely mediates AR development, suggesting that its inhibition represents a novel therapeutic strategy for AR. Copyright (c) 2021, Japanese Society of Allergology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).