Laboratoire de Recherche en Inflammation des Granulocytes, Université du Québec Institut National de la Recherche Scientifique, Institut Armand-Frappier, Laval, Québec, Canada.
PLoS One. 2013 Aug 19;8(8):e72138. doi: 10.1371/journal.pone.0072138. eCollection 2013.
S100A8 and S100A9 are cytoplasmic proteins expressed by phagocytes. High concentrations of these proteins have been correlated with various inflammatory conditions, including autoimmune diseases such as rheumatoid arthritis and Crohn's disease, as well as autoinflammatory diseases. In the present study, we examined the effects of S100A8 and S100A9 on the secretion of cytokines and chemokines from PBMCs. S100A8 and S100A9 induced the secretion of cytokines such as IL-6, IL-8, and IL-1β. This secretion was associated with the activation and translocation of the transcription factor NF-κB. Inhibition studies using antisense RNA and the pharmacological agent BAY-117082 confirmed the involvement of NF-κB in IL-6, IL-8, and IL-1β secretion. S100A8- and S100A9-mediated activation of NF-κB, the NLR family, pyrin domain-containing 3 (NLRP3) protein, and pro-IL-1β expression was dependent on the generation of reactive oxygen species. This effect was synergistically enhanced by ATP, a known inflammasome activator. These results suggest that S100A8 and S100A9 enhance the inflammatory response by inducing cytokine secretion of PBMCs.
S100A8 和 S100A9 是吞噬细胞表达的细胞质蛋白。这些蛋白质的高浓度与各种炎症状态相关，包括自身免疫性疾病，如类风湿关节炎和克罗恩病，以及自身炎症性疾病。在本研究中，我们研究了 S100A8 和 S100A9 对 PBMC 细胞因子和趋化因子分泌的影响。S100A8 和 S100A9 诱导细胞因子如 IL-6、IL-8 和 IL-1β 的分泌。这种分泌与转录因子 NF-κB 的激活和易位有关。使用反义 RNA 和药理学试剂 BAY-117082 的抑制研究证实了 NF-κB 在 IL-6、IL-8 和 IL-1β 分泌中的参与。S100A8 和 S100A9 介导的 NF-κB、NLR 家族、pyrin 结构域包含 3（NLRP3）蛋白和 pro-IL-1β 表达的激活依赖于活性氧的产生。这种作用通过已知的炎症小体激活剂 ATP 协同增强。这些结果表明，S100A8 和 S100A9 通过诱导 PBMC 细胞因子分泌来增强炎症反应。
