IL-32, a novel cytokine with a possible role in disease

IL-32, a novel cytokine with a possible role in disease
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DOI:
10.1136/ard.2006.058511
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发表时间:
2006-11-01
影响因子:
27.4
通讯作者:
Kim, S-H
Kim, S-H
中科院分区:
医学1区
文献类型:
--
作者:
Dinarello, C. A.;Kim, S-H

文献摘要

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IL-32是13年前在IL-2激活的T淋巴细胞和自然杀伤细胞中首次报道的NK 4转录物的名称,功能未知。新的细胞因子有六种亚型。在一项从人尿液中分离可溶形式的IL-32受体的研究中,IL-32 α以高亲和力结合蛋白酶-3,并且不受酶抑制的影响。IL-32 α/IL-32 γ表达为重组分子。该细胞因子表现出促炎细胞因子的特性,并且还诱导抑制性κ B的降解和促分裂原活化蛋白p38的磷酸化。针对IL-32的单克隆抗体鉴定其在来自疾病状态的多种人类组织中的存在。来自健康受试者的上皮细胞表达低水平的细胞因子,但在诸如慢性阻塞性肺病、克罗恩病和银屑病的疾病状况中,表达显著增加。IL-32是体外用IFN γ刺激的上皮细胞中基因阵列研究中的主要转录物。在类风湿性关节炎中,滑液组织中IL-32的含量增加,这与疾病的严重程度相关。已观察到IL-32阳性的滑膜和巨噬细胞数量与红细胞沉降、IL-1 β、肿瘤坏死因子α和IL-18水平之间存在高度显著相关性。因此,IL-32表现出促炎性细胞因子的许多特性并与疾病严重程度相关。
IL-32 is the name given to the NK4 transcript first reported in IL-2 activated T lymphocytes and natural killer cells 13 years ago without known function. The novel cytokine has six isoforms. In an study to isolate a soluble form of the IL-32 receptor from human urine, IL-32 alpha bound proteinase-3 with high affinity and was not affected by enzyme inhibition. IL32 alpha/IL-32 gamma were expressed as recombinant molecules. The cytokine exhibits properties characteristic of proinflammatory cytokines and also induces the degradation of inhibitory kappa B and phosphorylation of mitogen activated protein p38. Monoclonal antibodies to IL-32 identify its presence in a variety of human tissues from diseases states. Epithelial cells from healthy subjects express low levels of the cytokine, but in disease conditions such as chronic obstructive pulmonary disease, Crohn's disease and psoriasis, the expression increases markedly. IL-32 is a major transcript in gene array studies in epithelial cells stimulated with IFN gamma in vitro. In rheumatoid arthritis, synovial tissues reveals increased content of IL-32, which correlates with severity of disease. A highly significant correlation has been observed between the number of synovial and macrophagic cells positive for IL-32 and the level of erythrocytes sedimentation, IL-1 beta, tumour necrosis factor alpha, and IL-18. Thus, IL-32 exhibits many properties of proinflammatory cytokines and associations with disease severity.