Renzi P M, al Assaad A S, Yang J, Yasruel Z, Hamid Q
Department of Medicine and Pathology, Meakins Christie Labs, Royal Victoria Hospital, McGill University, Montréal, Québec, Canada.
Am J Respir Cell Mol Biol. 1996 Sep;15(3):367-73. doi: 10.1165/ajrcmb.15.3.8810641.
To assess whether Th-2 cytokines are involved in the late airway response (LR) after antigen challenge, we evaluated cytokine mRNA expression in the lungs of two strains of rats before and 8 h after saline or antigen challenge: Brown Norway (BN) rats, high IgE producers that develop LR after antigen challenge and Sprague-Dawley (SD) rats, low IgE producers that develop little LR and no increased airway responsiveness after antigen challenge. Rats were sensitized with ovalbumin (OA) and 14 days later, lungs were obtained before or after OA challenge and measurement of lung physiology for 8 h. Lung tissue was either fixed for in situ hybridization or frozen for evaluation of mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). We examined mRNA expression for interleukin-4 (IL-4), and IL-5 (Th-2 cytokines) and IL-2 and interferon gamma (IFN-gamma, Th-1 cytokines). In situ hybridization showed that cells expressing IL-4 and -5 mRNA were increased in the airways of the lungs of BN rats after OA challenge (P < 0.05) and that cells expressing mRNA for IFN-gamma and IL-2 were higher in SD than in BN rats after antigen challenge (P < 0.05). Results from PCR showed that prior to antigen challenge, BN rats expressed in their lungs mRNA for IL-4 and -5 and SD rats expressed very little mRNA for IL-5 only. After antigen challenge most BN and SD rats expressed mRNA for IL-4 and -5 but expression of mRNA for IL-2 and IFN-gamma was only found in SD rats. In conclusion, rats that develop a LR after antigen challenge preferentially increase Th-2 cytokine expression in their lungs whereas those without LRs preferentially express Th-1 cytokines. Our results support the role of Th-2 cytokines in the LR and asthma.
为了评估Th-2细胞因子是否参与抗原激发后的迟发性气道反应(LR),我们在生理盐水或抗原激发前及激发后8小时,评估了两种品系大鼠肺组织中细胞因子mRNA的表达:褐家鼠(BN),高IgE产生者,抗原激发后会发生LR;斯普拉格-道利大鼠(SD),低IgE产生者,抗原激发后很少发生LR且气道反应性无增加。大鼠用卵清蛋白(OA)致敏,14天后,在OA激发前或激发后获取肺组织,并测量8小时的肺生理学指标。肺组织要么固定用于原位杂交,要么冷冻用于通过逆转录-聚合酶链反应(RT-PCR)评估mRNA表达。我们检测了白细胞介素-4(IL-4)、IL-5(Th-2细胞因子)以及IL-2和干扰素γ(IFN-γ,Th-1细胞因子)的mRNA表达。原位杂交显示,OA激发后,BN大鼠肺气道中表达IL-4和-5 mRNA的细胞增加(P < 0.05),且抗原激发后,SD大鼠中表达IFN-γ和IL-2 mRNA的细胞高于BN大鼠(P < 0.05)。PCR结果显示,在抗原激发前,BN大鼠肺中表达IL-4和-5的mRNA,而SD大鼠仅表达很少的IL-5 mRNA。抗原激发后,大多数BN和SD大鼠表达IL-4和-5的mRNA,但仅在SD大鼠中发现了IL-2和IFN-γ mRNA的表达。总之,抗原激发后发生LR的大鼠肺中Th-2细胞因子表达优先增加,而未发生LR的大鼠优先表达Th-1细胞因子。我们的结果支持Th-2细胞因子在LR和哮喘中的作用。