Recombinant bovine S100A8 and A9 enhance IL-1β secretion of interferon-gamma primed monocytes
Recombinant bovine S100A8 and A9 enhance IL-1β secretion of interferon-gamma primed monocytes
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DOI：
10.1016/j.vetimm.2013.07.002
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发表时间：
2013-09-15
影响因子：
1.8
通讯作者：
Schuberth, Hans-Joachim
中科院分区：
文献类型：
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作者：
Koy, Mirja;Hambruch, Nina;Schuberth, Hans-Joachim
在炎症组织中发现高水平的钙粒蛋白A （S100A8）和B （S100A9）与急性和慢性炎症性疾病有关。钙粒蛋白作为损伤相关分子模式（DAMPs）被讨论。为了分析calgranulins在炎症反应中的作用，我们克隆了牛S100A8和S100A9，成功表达并进行了hplc纯化。在botlr4转染的HEK293细胞中，这两种分子都不会诱导NF-kappa B活化，用这两种蛋白刺激牛单核细胞也不会导致白细胞介素1 β (IL-1 β)分泌或某些基因（IL1B、TNF、CXCL8、IL10、IL12） mRNA表达上调。然而，干扰素γ (ifn - γ)引发的牛单核细胞在S100A8、S100A9刺激以及与三磷酸腺苷（ATP）共同刺激后释放了大量的IL-1 β。在IL-4/ il -13引物单核细胞中，IL-1 β的释放完全被消除。结果表明，TLR4/MyD88/NF-kappa b独立的S100A8/ a9介导的炎症小体激活在Th1环境下更有利，S100A8和S100A9在牛中起到了DAMP的作用。(C) 2013 Elsevier B.V.版权所有
Calgranulin A (S100A8) and B (S100A9) are found at high levels in inflamed tissue and have been associated with acute and chronic inflammatory disorders. Calgranulins are discussed as damage-associated molecular patterns (DAMPs). To analyze the role of calgranulins for inflammatory responses, bovine S100A8 and S100A9 were cloned, successfully expressed and FPLC-purified. Both molecules did not induce NF-kappa B activation in boTLR4-transfected HEK293 cells and stimulation of bovine monocytes with both proteins did not result in interleukin 1 beta (IL-1 beta) secretion or an upregulated mRNA expression of selected genes (IL1B, TNF, CXCL8, IL10, IL12). However, Interferon gamma (IFN-gamma) primed bovine monocytes released significantly higher amounts of IL-1 beta after stimulation with S100A8, S100A9, and co-stimulation with adenosine triphosphate (ATP). In IL-4/IL-13-primed monocytes, the IL-1 beta release was completely abrogated. The results imply that TLR4/MyD88/NF-kappa B-independent S100A8/A9-mediated activation of the inflammasome in cattle is favored in a Th1 environment and that S100A8 and S100A9 act as a DAMP in cattle. (C) 2013 Elsevier B.V. All rights reserved.