Christopherson Kent W, Hromas Robert A
Department of Microbiology/Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Curr Pharm Des. 2004;10(2):145-54. doi: 10.2174/1381612043453405.
Compelling evidence now exists supporting the involvement of chemokines in the pathogenesis of autoimmune diseases. Examples of chemokines and chemokine receptors being involved in mediating autoimmune disease exist for rheumatoid arthritis, multiple sclerosis, allograft rejection, systemic lupus erythematosus, psoriasis, atopic dermatitis, lichen planus, and graft-versus-host-disease. Expression of chemokines by endothelial cells appears to be an important step in the development of these diseases. Since chemokines are small molecular weight molecules that act through G-protein coupled receptors, they make attractive drug targets. Several antagonists of chemokine - chemokine receptor interactions have been used to successfully alleviate some or all of the symptoms associated with many of these diseases in animal models. Further investigation of the involvement of chemokines in the pathogenesis or progression of autoimmune diseases may lead to practical clinical advances in diagnosis, prognosis, and therapy of such diseases.
目前已有确凿证据支持趋化因子参与自身免疫性疾病的发病机制。在类风湿性关节炎、多发性硬化症、同种异体移植排斥反应、系统性红斑狼疮、银屑病、特应性皮炎、扁平苔藓和移植物抗宿主病中,都存在趋化因子和趋化因子受体参与介导自身免疫性疾病的例子。内皮细胞表达趋化因子似乎是这些疾病发展过程中的一个重要步骤。由于趋化因子是通过G蛋白偶联受体起作用的小分子重量分子,它们成为有吸引力的药物靶点。在动物模型中,几种趋化因子-趋化因子受体相互作用的拮抗剂已被用于成功缓解与许多此类疾病相关的部分或全部症状。进一步研究趋化因子在自身免疫性疾病发病机制或进展中的作用,可能会在这些疾病的诊断、预后和治疗方面取得实际的临床进展。