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白细胞介素-32γ特异性单克隆抗体及白细胞介素-32特异性酶联免疫吸附测定的研发

Interleukin-32 gamma specific monoclonal antibody and developing IL-32 specific ELISA.

作者信息

Lee Siyoung, Kim Sunjong, Bae Suyoung, Choi Jida, Hong Jaewoo, Ryoo Soyoon, Jhun Hyunjhung, Hong Kwangwon, Kim Eunsom, Jo Seunghyun, Her Erk, Kim Soohyun

机构信息

Department of Immunology, College of Medicine, Konkuk University, Chungju City, Chungbuk, Korea.

出版信息

Hybridoma (Larchmt). 2010 Dec;29(6):501-9. doi: 10.1089/hyb.2010.0059. Epub 2010 Nov 18.

DOI:10.1089/hyb.2010.0059
PMID:21087097
Abstract

Cytokines are essential coordinators of defensive immune responses for resolving the invasion of pathogens such as bacteria, virus, and fungi. However, dysregulated cytokines are the main cause of various autoinflammatory immune disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Interleukin-32 (IL-32) is a recently described cytokine and characterized as a proinflammatory cytokine. IL-32 stimulates monocytes and macrophages to induce important proinflammatory cytokines (IL-1β, IL-6, and TNFα) and chemokines (IL-8 and MIP-2) by activating the NF-κB and p38 mitogen-activated protein (MAP) kinase pathways. The biological activities of IL-32 are associated with epidemic pathogens, Mycobacterium tuberculosis, influenza A virus, and human immunodeficiency virus (HIV). IL-32 is transcribed as six alternative splice variants (α, β, γ, δ, ɛ, and ζ), with IL-32γ being the most active isoform. However, it is unclear which isoform is related to specific disease activities since there are no high quality antibodies available to measure circulating IL-32 in biological samples of patients. Therefore, we developed specific anti-human IL-32γ monoclonal antibodies from recombinant human IL-32γ, which was expressed in Escherichia coli. The IL-32γ specific monoclonal antibodies recognized IL-32 in cell culture supernatants and serum of IL-32γ transgenic mice. The newly developed IL-32γ monoclonal antibodies will be a useful tool to measure IL-32 level in serum samples of various inflammatory diseases. These monoclonal antibodies will be helpful in investigating the precise function of IL-32 in immune responses and in autoinflammatory diseases.

摘要

细胞因子是防御性免疫反应的重要协调者,可消除细菌、病毒和真菌等病原体的入侵。然而,细胞因子失调是类风湿性关节炎、炎症性肠病和牛皮癣等各种自身炎症性免疫疾病的主要原因。白细胞介素-32(IL-32)是最近描述的一种细胞因子,被表征为促炎细胞因子。IL-32通过激活NF-κB和p38丝裂原活化蛋白(MAP)激酶途径,刺激单核细胞和巨噬细胞诱导重要的促炎细胞因子(IL-1β、IL-6和TNFα)和趋化因子(IL-8和MIP-2)。IL-32的生物学活性与流行性病原体、结核分枝杆菌、甲型流感病毒和人类免疫缺陷病毒(HIV)有关。IL-32转录为六种可变剪接变体(α、β、γ、δ、ɛ和ζ),其中IL-32γ是最具活性的异构体。然而,由于没有高质量的抗体可用于测量患者生物样品中的循环IL-32,尚不清楚哪种异构体与特定疾病活动相关。因此,我们从在大肠杆菌中表达的重组人IL-32γ开发了特异性抗人IL-32γ单克隆抗体。IL-32γ特异性单克隆抗体可识别IL-32γ转基因小鼠细胞培养上清液和血清中的IL-32。新开发的IL-32γ单克隆抗体将成为测量各种炎症性疾病血清样品中IL-32水平的有用工具。这些单克隆抗体将有助于研究IL-32在免疫反应和自身炎症性疾病中的精确功能。

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Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus.
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Inducible interleukin 32 (IL-32) exerts extensive antiviral function via selective stimulation of interferon λ1 (IFN-λ1).诱导型白细胞介素 32(IL-32)通过选择性刺激干扰素 λ1(IFN-λ1)发挥广泛的抗病毒功能。
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Antitumor activity of IL-32β through the activation of lymphocytes, and the inactivation of NF-κB and STAT3 signals.IL-32β 通过激活淋巴细胞,以及使 NF-κB 和 STAT3 信号失活来发挥抗肿瘤活性。
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