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在小鼠哮喘模型中,联合使用CpG寡核苷酸和藜提取物可逆转IgG2a/IgG1比例,并增加IFN-γ和IL-10的产生。

Co-administration of CpG oligonucleotides and chenopodium album extract reverse IgG2a/IgG1 ratios and increase IFN-gamma and IL-10 productions in a murine model of asthma.

作者信息

Mousavi Tahereh, Salek Moghadam Alireza, Falak Reza, Tebyanian Majid

机构信息

Immunology Department, Iran University of Medical Sciences, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2008 Mar;7(1):1-6.

Abstract

Asthma is a disorder of increasing severity and prevalence. Recent knowledge about the pathogenesis of asthma emphasizes its inflammatory nature. CpG oligonucleotides are a class of compounds containing motifs based on the cytosine-guanine dinucleotides (CpG-ODNs). These motifs are suppressed in mammalian DNA. They induce inflammation in mammals characterized by the induction of T helper type 1 and regulatory responses. In this paper, the effect of CpG DNA co-administration with a homemade Chenopodium album (Ch.a) extract in a murine model of asthma is reported for the first time. Balb/C mice were sensitized using Ch.a. pollen allergenic extract plus CpG-ODNs intraperitoneally and were challenged with aerosolized allergen. Results measured included IL-10 and IFN-gamma cytokines as well as IgG subclasses. For this, splenocytes from mice treated with CpG/Ag or Ag alone, were cultured in the presence of antigen. The results showed that CpG ODN administered at the time of Ch.a sensitization, effectively increased cytokines and IgG2a/IgG1 ratios compared with those in mice treated with antigen or with PBS alone(P<or= 0.001). Our experiments revealed that Ch.a. sensitization decreased IgG2a/IgG1 compared with non-sensitized mice (P<or= 0.001), while CpG ODN/Ch.a reversed this ratio, indicating CpG potentials towards IgG2a subclass switching.We conclude that Co- administration of Ch.a. allergen and CpG ODN prevents the development of TH2-mediated response probably through the IL-10 regulatory effects. Thus, these components could be used with the other allergens in order to induce the prevention of inflammatory conditions. We suggest further studies are necessary to identify the potential effects of CpG-ODNs administration in conjunction with other antigens prepared from the regional allergens in Iran. Taken together, we suppose that the results obtained in this study in animal models may be useful in human trials conducted by other investigators.

摘要

哮喘是一种严重程度和患病率不断增加的疾病。最近关于哮喘发病机制的知识强调了其炎症性质。CpG寡核苷酸是一类基于胞嘧啶-鸟嘌呤二核苷酸(CpG-ODN)基序的化合物。这些基序在哺乳动物DNA中受到抑制。它们在哺乳动物中诱导炎症,其特征是诱导1型辅助性T细胞和调节性反应。本文首次报道了在哮喘小鼠模型中,CpG DNA与自制的藜(Ch.a)提取物共同给药的效果。用Ch.a花粉变应原提取物加CpG-ODN对Balb/C小鼠进行腹腔致敏,并用雾化变应原进行激发。测量的结果包括IL-10和IFN-γ细胞因子以及IgG亚类。为此,将用CpG/抗原或单独用抗原处理的小鼠的脾细胞在抗原存在下培养。结果表明,与单独用抗原或PBS处理的小鼠相比,在Ch.a致敏时给予CpG ODN可有效增加细胞因子和IgG2a/IgG1比值(P≤0.001)。我们的实验表明,与未致敏小鼠相比,Ch.a致敏降低了IgG2a/IgG1比值(P≤0.001),而CpG ODN/Ch.a逆转了该比值,表明CpG具有促进IgG2a亚类转换的潜力。我们得出结论,Ch.a变应原和CpG ODN共同给药可能通过IL-10调节作用预防TH2介导的反应。因此,这些成分可与其他变应原一起使用,以预防炎症状态。我们建议有必要进一步研究,以确定CpG-ODN与伊朗地区变应原制备的其他抗原联合给药的潜在效果。综上所述,我们认为本研究在动物模型中获得的结果可能对其他研究人员进行的人体试验有用。

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