Japan Animal Specialty Medical Institute, Tsuzuki, Yokohama, Japan.
Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan.
Front Immunol. 2022 Apr 20;13:863309. doi: 10.3389/fimmu.2022.863309. eCollection 2022.
Cardiac fibroblasts participate in the inflammatory process of heart diseases as sentinel cells of the cardiac tissue. In this study, we investigated the effect of the proinflammatory cytokine, interleukin 1β (IL-1β), on the expression of interleukin 8 (IL-8), which contributes to the induction of innate immunity the activation and recruitment of innate immune cells, such as neutrophils, to the site of inflammation in canine cardiac fibroblasts. IL-1β mediates IL-8 mRNA expression and protein release in a dose- and time-dependent manner. The IL-β-mediated IL-8 protein release and mRNA expression were inhibited by 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide, an inhibitor of the transcription factor, nuclear factor (NF)-κB. In cells treated with IL-1β, NF-κB p65 and p105 were transiently phosphorylated, indicating the activation of NF-κB. However, IL-1β failed to induce IL-8 mRNA expression in the cells transfected with p65 small interfering RNA (siRNA), but not in those transfected with p105 siRNA. These observations suggest that IL-1β induces IL-8 expression the activation of NF-κB p65 in canine cardiac fibroblasts.
心肌成纤维细胞作为心脏组织的哨兵细胞，参与心脏疾病的炎症过程。在这项研究中，我们研究了促炎细胞因子白细胞介素 1β（IL-1β）对白细胞介素 8（IL-8）表达的影响，IL-8 有助于先天免疫的诱导和固有免疫细胞（如中性粒细胞）向犬心肌成纤维细胞炎症部位的激活和募集。IL-1β以剂量和时间依赖的方式介导 IL-8 mRNA 表达和蛋白释放。转录因子核因子（NF）-κB 的抑制剂 2-[[氨基羰基]氨基]-5-（4-氟苯基）-3-噻吩甲酰胺抑制了 IL-β介导的 IL-8 蛋白释放和 mRNA 表达。在接受 IL-1β 处理的细胞中，NF-κB p65 和 p105 被短暂磷酸化，表明 NF-κB 被激活。然而，IL-1β未能诱导转染 p65 小干扰 RNA（siRNA）的细胞中 IL-8 mRNA 的表达，但转染 p105 siRNA 的细胞则可以。这些观察结果表明，IL-1β诱导犬心肌成纤维细胞中 IL-8 表达和 NF-κB p65 的激活。
