Interleukin-18 (IFNγ-inducing factor) induces IL-8 and IL-1β via TNFα production from non-CD14+ human blood mononuclear cells
Interleukin-18 (IFNγ-inducing factor) induces IL-8 and IL-1β via TNFα production from non-CD14+ human blood mononuclear cells
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DOI：
10.1172/jci1379
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发表时间：
1998-02-01
影响因子：
15.9
通讯作者：
Dinarello, CA
中科院分区：
文献类型：
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作者：
Puren, AJ;Fantuzzi, G;Dinarello, CA
IL-18是作为前体分子合成的，没有信号肽，但需要IL-1 β转化酶表达、纯化人前体IL-18，并通过ICE切割成18-kD成熟形式，成熟IL-18诱导的IL-8，巨噬细胞炎性蛋白-1 α，和单核细胞趋化蛋白-1。用IL-1受体拮抗剂阻断IL-1导致IL-8减少50%，用TNF结合蛋白中和TNF导致IL-1 β减少66%，IL-8减少80%，平均TNF α mRNA减少88%。在纯化的CD 14（+）细胞中，而不是CD 3（+）/CD 4（+）中，IL-18诱导IL-8和IL-1 β的基因表达和合成，在非CD 14（+）群体中诱导TNF α的产生，并且IL-18不诱导TNF β。在纯化的自然杀伤细胞中，IL-18诱导的IL-8也被TNF结合蛋白抑制，IL-18不诱导TNF α细胞因子、IL-1 Ra或IL-10，尽管IL-10抑制了IL-18诱导的TNF α，但在IFN γ存在下，IL-18诱导的TNF α增强，并且成熟形式的IL-1 β增加，我们的结论是，IL-18通过直接刺激基因表达和从CD 3（+）/CD 4（+）和自然杀伤细胞合成TNF α，随后产生IL-18而具有促炎特性。1 β和IL-8。
IL-18 is synthesized as a precursor molecule without a signal peptide but requires the IL-1 beta converting enzyme (ICE, caspase-1) for cleavage into a mature peptide, Human precursor IL-18 was expressed, purified, and cleaved by ICE into a 18-kD mature form, Mature IL-18 induced IL-8, macrophage inflammatory protein-1 alpha, and monocyte chemotactic protein-1 in human peripheral blood mononuclear cells in the absence of any co-stimuli, Blocking IL-1 with IL-1 receptor antagonist resulted in a 50% reduction in IL-8, Neutralization of TNF with TNF binding protein resulted in a 66% reduction in IL-1 beta, an 80% reduction of IL-8, and an 88% reduction in mean TNF alpha mRNA, In purified CD14(+) cells but not CD3(+)/CD4(+), IL-18 induced gene expression and synthesis of IL-8 and IL-1 beta, TNF alpha production was induced in the non-CD14(+) population and there was no induction of TNF beta by IL-18, In purified natural killer cells, IL-18 induced IL-8 that was also inhibited by TNF binding protein, IL-18 did not induce antiinflammatory cytokines, IL-1Ra, or IL-10, although IL-18 induction of TNF alpha was inhibited by IL-10, In the presence of IFN gamma, IL-18-induced TNF alpha was enhanced and there was an increase in the mature form of IL-1 beta, We conclude that IL-18 possesses proinflammatory properties by direct stimulation of gene expression and synthesis of TNF alpha from CD3(+)/CD4(+) and natural killer cells with subsequent production of IL-1 beta and IL-8 from the CD14(+) population.