Kim Soo-Hyun, Han Sun-Young, Azam Tania, Yoon Do-Young, Dinarello Charles A
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Immunity. 2005 Jan;22(1):131-42. doi: 10.1016/j.immuni.2004.12.003.
We describe the gene structure, regulation, signal transduction. and functions of a cytokine, interleukin (IL)-32. An IL-18 unresponsive cell was converted to a responsive cell by transfection of the IL-18 receptor beta chain, and IL-18-induced microarray revealed high expression of a cytokine-like gene. Although IL-32 does not share sequence homology with known cytokine families, IL-32 induces various cytokines, human TNFalpha, and IL-8 in THP-1 monocytic cells as well as mouse TNFalpha and MIP-2 in Raw macrophage cells. IL-32 activates typical cytokine signal pathways of nuclear factor-kappa B (NF-kappaB) and p38 mitogen-activated protein kinase. IL-32 mRNA is highly expressed in immune tissue rather than other tissues. Human IL-32 exists as four splice variants, and IL-32 from other species were found as expressed sequence tag clones in the databank. Induced in human peripheral lymphocyte cells after mitogen stimulation, in human epithelial cells by IFNgamma, and in NK cells after exposure to the combination of IL-12 plus IL-18, IL-32 may play a role in inflammatory/autoimmune diseases.
我们描述了一种细胞因子白细胞介素（IL）-32的基因结构、调控、信号转导及功能。通过转染IL-18受体β链，将一株对IL-18无反应的细胞转变为有反应的细胞，并且IL-18诱导的基因芯片显示一种细胞因子样基因高表达。尽管IL-32与已知的细胞因子家族没有序列同源性，但IL-32可在THP-1单核细胞中诱导多种细胞因子、人肿瘤坏死因子α（TNFα）和IL-8，以及在Raw巨噬细胞中诱导小鼠TNFα和巨噬细胞炎性蛋白-2（MIP-2）。IL-32激活核因子κB（NF-κB）和p38丝裂原活化蛋白激酶的典型细胞因子信号通路。IL-32 mRNA在免疫组织中而非其他组织中高表达。人IL-32以四种剪接变体形式存在，并且在数据库中发现其他物种的IL-32为表达序列标签克隆。在有丝分裂原刺激后人外周淋巴细胞中、在γ干扰素刺激后人上皮细胞中以及在暴露于IL-12加IL-18组合后自然杀伤细胞中被诱导，IL-32可能在炎症/自身免疫性疾病中发挥作用。
