J Inflamm Res:新研究鉴定了BX471对变应性鼻炎的治疗作用

2020-09-10 AlexYang MedSci原创

变应性鼻炎(AR)是一种免疫球蛋白E (IgE)介导的炎症性呼吸过敏,其特征是Th2细胞因子升高和炎症细胞向鼻组织浸润。BX471是一种小分子C-C趋化因子受体1型(CCR1)拮抗剂,它通过阻断初级配

变应性鼻炎(AR)是一种免疫球蛋白E (IgE)介导的炎症性呼吸过敏,其特征是Th2细胞因子升高和炎症细胞向鼻组织浸润。BX471是一种小分子C-C趋化因子受体1型(CCR1)拮抗剂,它通过阻断初级配体参与炎症的抑制。在本研究中,来自东北农业大学、华中农业大学等的科学家在卵白蛋白(OVA)诱导的AR小鼠模型中检测了BX471的抗炎作用。

研究人员采用酶联免疫吸附法(ELISA)检测了OVA特异性IgE和Th1细胞因子水平,并通过RT-qPCR检测促炎介质鼻部表达。随后用苏木精、伊红(HE)和PAS染色鼻腔切片,研究伊红细胞浸润和杯状细胞上皮化生。此外还通过Western Blot检测了NF-kB、TLR4和TLR2的相对蛋白水平,用流式细胞术测定CD4+CD25+Foxp3+ T调节性细胞(Treg)的百分率。

结果显示,用BX471治疗的小鼠喷嚏和鼻摩擦行为明显减轻。BX471显著下调了鼻部促炎因子的表达,抑制了肿瘤坏死因子α(TNF-α)和NF-kB的蛋白水平。CCR1配体的阻断抑制了鼻腔嗜酸性粒细胞的招募。此外,在BX471治疗的小鼠中,Treg细胞数量上调。

鼻黏膜组织学检查:A,D:健康组;B,E:空白对照组;C,F:BX47I治疗组

这些结果表明,BX471在小鼠AR模型中发挥了抗炎作用,其抑制CCR1介导的TNF抑制剂的产生,进而抑制炎症细胞中NF-kB的激活,导致Th2细胞因子、IL-1抑制因子、VCAM-1、GM-CSF、RANTES和MIP-1的表达水平下降,从而抑制鼻粘膜嗜酸性粒细胞募集。此外,BX-471可通过增加Treg细胞数量来发挥抗过敏作用。综上所述,BX471是一种很有前途的治疗AR的策略。

原始出处:

Suoyi Feng , Longzhu Ju , Ziqi Shao et al. Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis. J Inflamm Res. 2020

 

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