[Effect of extracellular cyclophilin A on inflammatory response and anti-inflammatory activity of antibody against cyclophilin A].
[Effect of extracellular cyclophilin A on inflammatory response and anti-inflammatory activity of antibody against cyclophilin A].
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DOI：
10.13345/j.cjb.170102
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发表时间：
2018-01-25
期刊：
影响因子：
--
通讯作者：
Sun, Lei
中科院分区：
文献类型：
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作者：
Li, Wenbo;Liu, Wei;Sun, Lei
亲环素A（Cyclophilin A，CypA）是肽基脯氨酸异构酶（PPIase）家族的一员。CypA是一种广泛分布的细胞内蛋白。它也被证明是由细胞分泌的炎症刺激和氧化应激反应。细胞外CypA（eCypA）与CD 147相互作用，通过将白细胞募集到炎症组织中来启动炎症反应。重组CypA在大肠杆菌中表达，然后使用Superdex 75 16/60纯化。Real-time PCR和ELISA结果显示，eCypA刺激BMDM后，BMDM细胞分泌的IL-1 β等促炎细胞因子的表达水平显著上调，表明eCypA在促进炎症反应中发挥重要作用。此外，使用纯化的CypA蛋白制备抗CypA抗体，用于在LPS诱导的急性肺部炎症的小鼠模型中的治疗评价。抗体处理的小鼠显示肺损伤减轻，肺组织和血液中IL-1 β的表达水平显著降低，表明抗CypA抗体发挥了有效的抗炎活性。我们的发现为炎症介导的疾病提供了潜在的治疗抗体。
Cyclophilin A (CypA) is a member of peptidyl prolylisomerases (PPIase) family. CypA is best known as a ubiquitously distributed intracellular protein. It has also been shown to be secreted by cells in response to inflammatory stimuli and oxidative stress. Extracellular CypA (eCypA) interacts with CD147 to initiate inflammatory responses via recruiting leucocytes into inflamed tissue. Recombinant CypA was expressed in Escherichia coli and then purified using Superdex 75 16/60. The results of Real-time PCR and ELISA showed that the expression levels of proinflammatory cytokines, such as IL-1beta, secreted by eCypA stimulated BMDM were significantly up-regulated, indicating that eCypA played an important role in promoting inflammatory responses. In addition, anti-CypA antibody was prepared using purified CypA protein for therapeutic evaluation in a mouse model of LPS-induced acute lung inflammation. Antibody-treated mice showed reduced lung injury and the expression levels of IL-1beta in the lung tissue and blood were decreased significantly, indicating that anti-CypA antibody exerted a potent anti-inflammatory activity. Our findings provide a potential therapeutic antibody for inflammation-mediated diseases.