Department of Clinical Laboratory, Jiangxi Provincial People's Hospital and Affiliated People's Hospital of Nanchang University, Nanchang, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University & Jiangxi Provincial Key Laboratory for Laboratory Medicine, Nanchang, China.
J Immunol Res. 2021 Mar 30;2021:6687555. doi: 10.1155/2021/6687555. eCollection 2021.
Clinically, severe bacterial infection can cause septicemia and multiple organ dysfunction syndrome, especially liver injury. CD38 is closely related to many inflammatory pathways, but its role in liver injury caused by bacterial infection remains unclear. The purpose of this study is to discuss the specific role of CD38 in bacterial liver injury. Eight-week-old male C57BL/6 mice (WT, CD38 and CD38TLR4) were used and stimulated with (ATCC25922) or PBS, intraperitoneally. After 3 hours of bacterial stimulation, serum was collected to detect ALT and AST concentration, and liver tissue was harvested for hematoxylin and eosin staining and bacterial culture. The mRNA expressions of TLR4, NLRP3, IL-1, IL-18, and GSDMD were quantitatively determined by RT-qPCR. The expressions of TLR4, MyD88, TRIF, NF-B p65, NLRP3, GSDMD, and cytokines were detected by Western blot. The expression and localization of ERK1/2 were detected by immunohistochemistry and Western blot. The results showed that bacterial stimulation could upregulate the expression of inflammatory cytokines, leading to hepatic dysfunction. Moreover, bacterial stimulation of CD38-deficient mice can aggravate the inflammatory response, the expressions of TLR4, NF-B, and ERK1/2 were significantly increased, and the biomarkers related to pyroptosis also manifested more obvious pyroptosis. However, TLR4 mutation significantly alleviated inflammation and pyroptosis in the liver caused by bacteria, on the basis of CD38 deficiency. Overall, CD38 knockout exacerbates bacteria-induced liver damage through TLR4-NLRP3-GSDMD-mediated pyroptosis.
临床上，严重细菌感染可引起败血症和多器官功能障碍综合征，尤其是肝损伤。CD38 与许多炎症途径密切相关，但它在细菌感染引起的肝损伤中的作用尚不清楚。本研究旨在探讨 CD38 在细菌性肝损伤中的具体作用。使用 8 周龄雄性 C57BL/6 小鼠（WT、CD38 和 CD38TLR4），经腹腔注射 （ATCC25922）或 PBS 刺激。细菌刺激 3 小时后，收集血清检测 ALT 和 AST 浓度，并采集肝组织进行苏木精和伊红染色和细菌培养。通过 RT-qPCR 定量测定 TLR4、NLRP3、IL-1、IL-18 和 GSDMD 的 mRNA 表达。通过 Western blot 检测 TLR4、MyD88、TRIF、NF-B p65、NLRP3、GSDMD 和细胞因子的表达。通过免疫组化和 Western blot 检测 ERK1/2 的表达和定位。结果表明，细菌刺激可上调炎症细胞因子的表达，导致肝功能障碍。此外，细菌刺激 CD38 缺陷小鼠可加重炎症反应，TLR4、NF-B 和 ERK1/2 的表达显著增加，与细胞焦亡相关的生物标志物也表现出更明显的细胞焦亡。然而，TLR4 突变在 CD38 缺陷的基础上显著减轻了细菌引起的肝脏炎症和细胞焦亡。综上所述，CD38 敲除通过 TLR4-NLRP3-GSDMD 介导的细胞焦亡加重细菌引起的肝损伤。
