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体内和体外过敏原激发后上呼吸道黏膜中转录因子GATA-3的上调。

Upregulation of the transcription factor GATA-3 in upper airway mucosa after in vivo and in vitro allergen challenge.

作者信息

Nakamura Y, Christodoulopoulos P, Cameron L, Wright E, Lavigne F, Toda M, Muro S, Ray A, Eidelman D H, Minshall E, Hamid Q

机构信息

Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.

出版信息

J Allergy Clin Immunol. 2000 Jun;105(6 Pt 1):1146-52. doi: 10.1067/mai.2000.107045.

Abstract

BACKGROUND

Allergic rhinitis is a complex upper airways disorder characterized by the infiltration of eosinophils and T(H2)-type T lymphocytes. GATA-3 is a novel transcription factor recently shown to regulate IL-5 and, possibly, IL-4 gene expression. We previously reported that GATA-3 is increased within the bronchial mucosa of allergic asthmatic subjects compared with control subjects.

OBJECTIVE

In the present study we set out to determine whether there is also an increased number of cells expressing GATA-3 messenger (m)RNA within the nasal mucosa of patients with allergic rhinitis.

METHODS

Inferior turbinate biopsy specimens were obtained from patients with allergic rhinitis and nonatopic control subjects before and after local allergen provocation in vivo. To assess the contribution of resident cells expressing GATA-3 mRNA, we also performed isolated explant studies in which nasal mucosal tissue from subjects with allergic rhinitis and nonatopic control subjects was cultured in allergen-treated medium. The presence of mRNA coding for GATA-3, IL-5, IL-4, IL-13, and GM-CSF was assessed by using in situ hybridization.

RESULTS

The number of GATA-3 mRNA(+) cells was increased after local allergen provocation in vivo (increase in GATA-3 mRNA(+) cells [mean +/- SEM]: subjects with allergic rhinitis, 11.3 +/- 8.7; control subjects, 1.2 +/- 4.1; P <.05) and in explanted nasal mucosa in vitro (subjects with allergic rhinitis, 10. 2 +/- 3.8; control subjects, 2.7 +/- 4.4; P <.05). The gene expression of GATA-3 was significantly correlated to the numbers of IL-5 (r = 0.87) and GM-CSF (r = 0.79) mRNA(+) cells but not with IL-4 or IL-13 mRNA(+) cells.

CONCLUSION

In summary, the expression of the transcription factor GATA-3 was increased after allergen challenge, and this was evident in the absence of de novo inflammatory cell recruitment. GATA-3 may be a potential target in the treatment of allergic diseases, such as rhinitis.

摘要

背景

变应性鼻炎是一种复杂的上呼吸道疾病,其特征为嗜酸性粒细胞和辅助性T细胞2(Th2)型T淋巴细胞浸润。GATA-3是一种新型转录因子,最近发现它可调节白细胞介素-5(IL-5),也可能调节IL-4的基因表达。我们之前报道过,与对照受试者相比,变应性哮喘患者支气管黏膜内的GATA-3水平升高。

目的

在本研究中,我们着手确定变应性鼻炎患者鼻黏膜内表达GATA-3信使核糖核酸(mRNA)的细胞数量是否也增加。

方法

在体内局部变应原激发前后,从变应性鼻炎患者和非特应性对照受试者获取下鼻甲活检标本。为评估表达GATA-3 mRNA的固有细胞的作用,我们还进行了离体组织研究,即将变应性鼻炎患者和非特应性对照受试者的鼻黏膜组织在变应原处理过的培养基中培养。通过原位杂交评估编码GATA-3、IL-5、IL-4、IL-13和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的mRNA的存在情况。

结果

体内局部变应原激发后,GATA-3 mRNA(+)细胞数量增加(GATA-3 mRNA(+)细胞增加数[平均值±标准误]:变应性鼻炎患者,11.3±8.7;对照受试者,1.2±4.1;P<0.05),体外培养的鼻黏膜中也是如此(变应性鼻炎患者,10.2±3.8;对照受试者,2.7±4.4;P<0.05)。GATA-3的基因表达与IL-5(r = 0.87)和GM-CSF(r = 0.79)mRNA(+)细胞数量显著相关,但与IL-4或IL-13 mRNA(+)细胞数量无关。

结论

总之,变应原激发后转录因子GATA-3的表达增加,且在无新生炎症细胞募集的情况下也很明显。GATA-3可能是变应性疾病(如鼻炎)治疗的潜在靶点。

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