Interferon-γ-mediated inhibition of eotaxin generation : a novel mechanism for regulation of eosinophilic inflammation

Eotaxin是一种特异性结合CC趋化因子受体（CCR）3的CC趋化因子，在嗜酸性粒细胞上优先表达。Eotaxin与嗜酸性粒细胞选择性积累的发病机制有关，这是过敏性炎症的一个特征。我们建立了抗eotaxin的单克隆抗体，并建立了高灵敏度的ELISA系统。我们的研究结果如下。1)干扰素-γ完全减弱eotaxin的产生。(Miyamasu等。Int。2)真皮成纤维细胞是eotaxin的主要细胞来源。(Miyamasu等。3)哮喘患者诱导痰中eotaxin水平升高与临床参数的关系。（Yamada et al.）4)干扰素γ不影响eotaxin mRNA的稳定性，提示其在翻译后水平上具有抑制作用。（Miyamasu， M.et al. manuscript in preparation）5)功能性嗜酸性粒细胞CXCR4在一定条件下可诱导成嗜酸性粒细胞。（Nagase等人）J.Immunol。《科学》杂志，2000；Nagase等人。J.Allergy中国。6)哮喘患者支气管上皮细胞表达Th-2特异性趋化因子胸腺及活化相关趋化因子（TARC）。（Sekiya等）J.Immunol。我们的研究结果表明，eotaxin是过敏性炎症的潜在治疗靶点。进一步研究干扰素-γ介导的eotaxin生成抑制的分子机制将有助于建立治疗过敏性疾病的新策略。

Eotaxin is a CC chemokine specifically binds to CC chemokine receptor (CCR)3, which is preferentially expressed on eosinophils. Eotaxin is implicated in pathogenesis of selective accumulation of eosinophils, which is a characteristic aspect of allergic inflammation. We established monoclonal antibodies against eotaxin and developed a high-sensitive ELISA system. Results of our research are follows.1) Interferon-γcompletely attenuates eotaxin generation. (Miyamasu M.et al. Int. Immunol. 11 : 1001-4, 1999)2) Dermal fibroblasts represent a major cellular source of eotaxin. (Miyamasu M.et al. Cytokine 11 : 751-8, 1999)3) Level of eotaxin is increased in association with clinical parameters in induced sputum of asthmatic patients. (Yamada H.et al. Allergy 55 : 1-6, 2000)4) Interferon-γ does not affect stability of eotaxin mRNA, indicating its inhibitory role at post-translational level. (Miyamasu, M.et al. manuscript in preparation)5) Functional eosinophil CXCR4 is inducible in eosinophils under certain conditions. (Nagase et al. J.Immunol. 164 : 5935-43, 2000 ; Nagase et al. J.Allergy Clin. Immunol. 106 : 1132-9, 2000)6) Bronchial epithelium of asthmatics intensely expresses a Th-2 specific chemokine thymus and activation-related chemokine (TARC). (Sekiya T.et al. J.Immunol. 165 : 2205-13, 2000)Our results indicate that eotaxin represents a potential therapeutic target for allergic inflammation. Further study dealing molecular mechanisms underlying interferon-γ-mediated inhibition of eotaxin generation will facilitate the establishment of a novel strategy for treatment of allergic disorders.