Koy Mirja, Hambruch Nina, Hussen Jamal, Pfarrer Christiane, Seyfert Hans-Martin, Schuberth Hans-Joachim
Immunology Unit, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, D-30173 Hannover, Germany.
Vet Immunol Immunopathol. 2013 Sep 15;155(3):162-70. doi: 10.1016/j.vetimm.2013.07.002. Epub 2013 Jul 12.
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-κB activation in boTLR4-transfected HEK293 cells and stimulation of bovine monocytes with both proteins did not result in interleukin 1β (IL-1β) secretion or an upregulated mRNA expression of selected genes (IL1B, TNF, CXCL8, IL10, IL12). However, Interferon γ (IFN-γ) primed bovine monocytes released significantly higher amounts of IL-1β after stimulation with S100A8, S100A9, and co-stimulation with adenosine triphosphate (ATP). In IL-4/IL-13-primed monocytes, the IL-1β release was completely abrogated. The results imply that TLR4/MyD88/NF-κB-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.
钙粒蛋白A（S100A8）和B（S100A9）在炎症组织中含量很高，并与急慢性炎症性疾病有关。钙粒蛋白被认为是损伤相关分子模式（DAMPs）。为了分析钙粒蛋白在炎症反应中的作用，克隆了牛源S100A8和S100A9，成功表达并通过快速蛋白质液相色谱（FPLC）进行了纯化。这两种分子在转染了牛TLR4（boTLR4）的人胚肾293（HEK293）细胞中均未诱导核因子κB（NF-κB）激活，用这两种蛋白刺激牛单核细胞也未导致白细胞介素1β（IL-1β）分泌或所选基因（IL1B、TNF、CXCL8、IL10、IL12）的mRNA表达上调。然而，经干扰素γ（IFN-γ）预处理的牛单核细胞在用S100A8、S100A9刺激以及与三磷酸腺苷（ATP）共同刺激后，释放出的IL-1β量显著更高。在经白细胞介素4/白细胞介素13（IL-4/IL-13）预处理的单核细胞中，IL-1β的释放完全被抑制。结果表明，在牛中，Toll样受体4/髓样分化因子88/核因子κB（TLR4/MyD88/NF-κB）非依赖性的S100A8/A9介导的炎性小体激活在Th1环境中更易发生，并且S100A8和S100A9在牛中作为一种损伤相关分子模式发挥作用。
