Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
Department of Tumor Pathology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
Inflammation. 2017 Oct;40(5):1717-1725. doi: 10.1007/s10753-017-0613-6.
Inflammatory response is required to proceed the optimal liver regeneration after liver injury. Recent reports demonstrated that inflammasomes are involved in the innate immune response. Several NOD-Like receptors (NLRs) participated in the formation of the inflammasomes. NACHT, LRR, and PYD domain-containing protein 3 (NALP3) belongs to the NLR families and recognizes adenosine triphosphate (ATP), crystals, and reactive oxygen species. The present study examined the effect of inflammasomes on the process of liver regeneration using NALP3 knockout (KO) mice. The activation of inflammasomes in the liver was induced after 70% partial hepatectomy (PHx). The liver-to-body weight ratio was significantly decreased in NALP3-KO mice compared to that in WT mice after PHx. The number of Ki67-positive cells and the expression of Cyclin D1 and E1 after PHx were reduced in NALP3-KO mice compared to WT mice. The expression of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) were decreased in the remnant liver of NALP3-KO mice compared to WT mice. Flow cytometric analysis revealed that the expression of chemokines was decreased and the accumulation of CD11b-positive cells was suppressed in NALP3-KO mice after PHx. The treatment with ATP, which is a ligand to NALP3, increased the liver-to-body weight ratio in WT mice. These results indicate that NALP3 signaling is required for the induction of inflammatory response and the development of liver regeneration after PHx.
炎症反应是肝损伤后进行最佳肝再生所必需的。最近的报告表明，炎性小体参与固有免疫反应。几种 NOD-样受体（NLRs）参与了炎性小体的形成。NACHT、LRR 和 PYD 结构域包含蛋白 3（NALP3）属于 NLR 家族，可识别三磷酸腺苷（ATP）、晶体和活性氧。本研究使用 NALP3 敲除（KO）小鼠检查炎性小体对肝再生过程的影响。在 70%部分肝切除术（PHx）后，肝脏中炎性小体的激活。与 WT 小鼠相比，PHx 后 NALP3-KO 小鼠的肝体比显著降低。与 WT 小鼠相比，PHx 后 NALP3-KO 小鼠的 Ki67 阳性细胞数和 Cyclin D1 和 E1 的表达减少。与 WT 小鼠相比，NALP3-KO 小鼠残肝中促炎细胞因子（IL-1β、TNF-α 和 IL-6）的表达减少。流式细胞术分析显示，PHx 后 NALP3-KO 小鼠趋化因子的表达减少，CD11b 阳性细胞的积累受到抑制。用 NALP3 的配体 ATP 处理可增加 WT 小鼠的肝体比。这些结果表明，NALP3 信号通路是 PHx 后诱导炎症反应和肝再生发展所必需的。
