巴基斯坦登革热患者hIL-6基因的分子克隆及原位杂交分析

Fariha Kanwal, A. Simair, Ting Chen, Yunlon Zhang, I. Qadri, Changrui Lu
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摘要

白细胞介素6 (IL-6)在哺乳动物宿主防御中具有重要的抗感染和组织损伤作用。其生物学功能明显丰富,包括造血、调节免疫反应、调节内分泌和神经系统、保护血浆蛋白、肝脏急性期蛋白和控制体温[1-3]。IL-6以广泛的方式作用于免疫和非免疫系统的细胞,通常表现得像一种影响体内平衡过程的激素。它的迅速诱导始于任何组织损伤或炎症的发生,激活宿主防御,并在组织稳态恢复时终止[4,5]。然而,在各种自身免疫性疾病、慢性炎症性疾病和癌症的发展中,IL-6的持续合成已被发现。使用人源化抗IL-6受体单克隆抗体的临床试验证实了IL-6阻断治疗难以控制的炎症性疾病的疗效,如全身性青少年特发性关节炎、类风湿性关节炎和Castleman病。细胞因子的情境依赖性和抗炎性使其成为临床干预的首选[7-10]。然而,IL-6有多种可选择的分子形式,具有多种模式的翻译后修饰,但其不同的细胞反应尚不清楚,来自细菌的重组IL-6没有修饰,复制了所有已知的功能,使得这些翻译后修饰对IL-6的不同作用没有导致作用[11,12]。
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Molecular Cloning and In Silico Analysis of hIL-6 Gene from Pakistani Dengue Hemorrhagic Fever Patients
Interleukin 6 (IL-6) is an important player against infections and tissue damage in mammalian host defense. Its biological functions are evidently spacious including hematopoiesis, modulation of immune response, regulation of endocrine and nervous systems, protective plasma proteins, acute-phase proteins by the liver and control of body temperature [1-3]. IL-6 works in an expansive manner on cells of the immune and nonimmune system and most often behave like a hormone affecting homeostatic processes. Its prompt induction starts with the onset of any tissue damage or inflammation, activating the host defense and terminates upon tissue homeostasis restoration [4,5]. However, the deregulated persistent synthesis of IL-6 has been seen in the development of various autoimmune, chronic inflammatory diseases and cancers [6]. Clinical trials using the humanized anti-IL-6 receptor monoclonal antibody have verified the efficacy of IL-6 blockade for the treatment of unmanageable inflammatory diseases, such as systemic juvenile idiopathic arthritis, rheumatoid arthritis, and Castleman’s disease. Its situation-dependent pro and anti-inflammatory nature makes cytokine as a top intention for clinical intervention [7-10]. However, IL-6 have several alternative molecular forms with multi-pattern post-translational modifications but its diverse cellular response is unclear and the recombinant IL-6 from bacteria without modifications reproducing all known functions left these post-translational modifications as non-causative for diverse actions of IL-6 [11,12].
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