As a disease with high mortality, many cytokines and signaling pathways are associated with sepsis. The pro-inflammatory cytokines and chemokines are participating in the pathogenesis of sepsis, especially in early stage. Moreover, the releases and expressions of cytokines are regulated by numerous signaling pathways, including TLR4/ERK pathway. But despite many studies have expounded the pathogenesis of sepsis and the regulation of cytokines in sepsis, how CD38 influence the expressions of related molecules in sepsis are still unknown. The aim of this study is illuminating the alteration of cytokines and signaling pathways in CD38^−/− mice injected with Escherichia coli. Compared with WT mice, E. coli infection results in more severe pulmonary injuries and higher mRNA expressions of cytokines. Compared with E. coli infected WT mice, CD38 knockout leads to aggravated pulmonary injury, increased phosphorylated ERK1/2, p38 and NF-κB p65, and enhanced levels of IL-1β, iNOS and MCP-1. While compared with E. coli infected CD38^−/− mice, TLR4 mutation results in alleviated pulmonary injury, down-regulated phosphorylated ERK1/2 and NF-κB p65, and decreased expressions of IL-1β and MCP-1. CD38 deficiency increased the expressions of IL-1β andMCP-1 and aggravated pulmonary injury through TLR4/ERK/NF-κB pathway in sepsis.

作为一种高死亡率的疾病，许多细胞因子和信号通路与脓毒症有关。促炎细胞因子和趋化因子参与了脓毒症的发病机制，尤其是在早期阶段。此外，细胞因子的释放和表达受多种信号通路的调节，包括TLR4/ERK通路。但尽管已有多项研究阐明了脓毒症的发病机制和脓毒症细胞因子的调控，但CD38如何影响脓毒症相关分子的表达仍是未知数。本研究的目的是阐明注射大肠杆菌的 CD38 ^-/-小鼠中细胞因子和信号通路的改变。与 WT 小鼠相比，大肠杆菌感染导致更严重的肺损伤和更高的细胞因子mRNA表达。与大肠杆菌感染的 WT 小鼠相比，CD38 敲除导致肺损伤加重，磷酸化 ERK1/2、p38 和 NF-κB p65 增加，IL-1β、iNOS 和 MCP-1 水平升高。与大肠杆菌感染的 CD38 ^-/-小鼠相比，TLR4 突变导致肺损伤减轻，磷酸化 ERK1/2 和 NF-κB p65 下调，IL-1β 和 MCP-1 表达降低。CD38缺乏增加了脓毒症患者IL-1β和MCP-1的表达，通过TLR4/ERK/NF-κB通路加重了肺损伤。