Christodoulopoulos P, Cameron L, Nakamura Y, Lemière C, Muro S, Dugas M, Boulet L P, Laviolette M, Olivenstein R, Hamid Q
Meakins-Christie Laboratories, McGill University, Sacré-Côeur Hospital, Laval University, Montreal, Quebec, Canada.
J Allergy Clin Immunol. 2001 Apr;107(4):586-91. doi: 10.1067/mai.2001.114883.
The expression of IL-4 and IL-5 is increased in patients with atopic asthma compared with control subjects and correlates with indices of pulmonary function. In nonatopic asthma the expression of IL-4, unlike IL-5, fails to correlate with pulmonary function, and compared with their atopic counterparts, these patients have fewer cells expressing IL-4 receptor (IL-4R). As such, a deficiency in the IL-4 signaling pathway may be implicated in nonatopic asthma. The transcription factors GATA-3 and cMAF mediate IL-4 and IL-5 synthesis, whereas signal transducer and activator of transcription 6 (STAT-6) is critical for IL-4R signaling.
This study examines the expression profile of these transcription factors in asthma, according to atopic status.
With immunocytochemistry, the expression of GATA-3, cMAF, and STAT-6 protein was determined in sections of bronchial biopsy specimens from patients with atopic asthma (n = 7), patients with nonatopic asthma (n = 8), and control subjects (n = 8).
Higher numbers of cells expressing GATA-3 and cMAF were observed in patients with atopic and those with nonatopic asthma than in control subjects and patients with tuberculosis (P <.001). There were also more STAT-6-immunoreactive cells in patients with atopic and those with nonatopic asthma than in control subjects (P <.0001, P <.05). Notably, however, fewer cells expressing STAT-6 protein were observed in nonatopic versus atopic asthma (P <.0001).
These results demonstrate the upregulation of GATA-3 and cMAF in both variants of asthma and indicate that reduced IL-4R signaling, because of lower STAT-6 expression, may be a feature of nonatopic asthma.
与对照受试者相比，特应性哮喘患者体内白细胞介素-4（IL-4）和白细胞介素-5（IL-5）的表达增加，且与肺功能指标相关。在非特应性哮喘中，IL-4的表达与肺功能无关，与特应性哮喘患者相比，这些患者表达IL-4受体（IL-4R）的细胞较少。因此，IL-4信号通路缺陷可能与非特应性哮喘有关。转录因子GATA-3和cMAF介导IL-4和IL-5的合成，而信号转导及转录激活因子6（STAT-6）对IL-4R信号传导至关重要。
本研究根据特应性状态，检测这些转录因子在哮喘中的表达谱。
采用免疫细胞化学法，测定特应性哮喘患者（n = 7）、非特应性哮喘患者（n = 8）和对照受试者（n = 8）支气管活检标本切片中GATA-3、cMAF和STAT-6蛋白的表达。
与对照受试者和肺结核患者相比，特应性哮喘患者和非特应性哮喘患者中表达GATA-3和cMAF的细胞数量更多（P <.001）。与对照受试者相比，特应性哮喘患者和非特应性哮喘患者中STAT-6免疫反应性细胞也更多（P <.0001，P <.05）。然而，值得注意的是，与特应性哮喘相比，非特应性哮喘中表达STAT-6蛋白的细胞较少（P <.0001）。
这些结果表明，两种类型的哮喘中GATA-3和cMAF均上调，且提示由于STAT-6表达较低导致的IL-4R信号传导减少可能是非特应性哮喘的一个特征。
