Interleukin 6 (IL-6) is a multifunctional cytokine that exerts its activities by binding to a high-affinity receptor complex consisting of two membrane glycoproteins: an 80 kDa ligand binding subunit (IL-6 R alpha /CD126) and a 130 kDa nonligand-binding signal-transducing subunit (gp130/CD130) (1‑4). The mouse IL-6 R alphacDNA encodes a precursor type I transmembrane protein of 460 amino acids (aa) that contains a 19 aa signal sequence, a 345 aa extracellular ligand binding domain, a 21 aa transmembrane region, and a 75 aa cytoplasmic segment (2). The extracellular segment contains an Ig-like and a fibronectin-type III domain, plus a membrane proximal WSXWS motif. In their extracellular regions, mouse IL-6 R alphashares 89%, 51% and 50% aa identity with rat, human and porcine IL-6 R alpha, respectively. Unlike gp130 that is expressed ubiquitously, the cellular distribution of IL-6 R alphais predominantly limited to hepatocytes and leukocyte subpopulations such as monocytes, neutrophils, T and B cells. Soluble IL-6 R alphahas been found in various body fluids (5). Two soluble receptor isoforms that arise either from proteolytic cleavage of the membrane-bound IL-6 R alpha, or by alternative mRNA splicing (reported only in human) have been described (6, 7). Soluble IL-6 R alphabinds IL-6 with an affinity similar to that of the membrane-bound IL-6 R alpha. More importantly, the soluble IL-6 R alpha /IL-6 complex is capable of interacting with the membrane-bound gp130 to activate cells that lack an integral membrane IL-6 R alpha. It has been documented that elevated soluble IL-6 R is associated with numerous diseases including arthritic lesions, multiple myeloma and Crohn’s disease (6, 7).
R&D Systems位于美国的明尼苏达州,一直致力于生物制品的开发与生产。公司成立之初主要生产用于医院及临床应用的血控品。1997年,公司推出第一个产品--富血小板血浆质控品;1981年,公司成为全球第二家生产含血小板全血控品的供应商。40多年的发展中,R&D Systems仍持续开发各种血控品产品。
1985年,作为公司推出的第一个科研试剂产品,也是全球第一家将该产品进行商业化生产的产品,R&D Systems成功上市了TGF-beta1蛋白。作为胞外信号分子,TGF-beta1蛋白在多种细胞中进行表达,并作为胞外信号分子参与免疫功能,细胞增殖和细胞分化等生物学过程。该产品推出后,公司陆续从生物材料中纯化了几种细胞因子产品并推向市场。
天然蛋白类产品的成功推广,加速了R&D Systems在细胞因子市场的开拓。公司于1985年形成Growth Factor事业部(现Biotechnology事业部)。Biotechnology事业部的目标是生产和营销重组人细胞因子。与天然来源提取蛋白相比较,DNA重组技术生产的蛋白产品其成本更低,产量更高,完全摆脱原料的限制。1989年,Biotechnology事业部开始开发抗细胞因子的单克隆和多克隆抗体,并于1990年开发了第一个ELISA试剂盒。
2014年2月10日,R&D Systems的母公司宣布命名为Bio-Techne. Bio-Techne旗下包括R&D Systems, Novus Biologicals, BiosPacific, Tocris Bioscience, Boston Biochem和Bionostics。