肠道上皮细胞exosomes抑制LPS诱导的炎症反应及其机制

As we know, many types of gut bacteria emit LPS, a very commonly found toxin, which might contribute to various inflammatory disorders, even endotoxin-induced septic shock. Intestinal epithelials and macrophages play great roles in maintaining the homeostasis. However, the mechanism of intestine protect against LPS-mediated inflammation is unclear. We found that intestinal epithelial exosomes play great roles on LPS-induced inflammatory response. In LPS-induced septic shock model, mice treated by intestinal epithelial exosomes displayed that their inflammatory response was alleviated and survival time was prolonged, and their bone marrow cell derived macrophages stimulated by LPS produced lower level of IL-6 and TNF-a, expressed lower level of MHC II and CD86. Based on the previous findings, in this study, we further investigate the biological function of intestinal epithelial exosomes on LPS-induced inflammation through different levels, such as cell, molecule, animal model and pathological tissue. Our studies may provide theoretical and experimental evidences supporting the application of intestinal epithelial exosomes as a new drug for clinical control and treatment of LPS-induced inflammation in future.

机体肠道内含有很多细菌并释放大量内毒素，这可能导致炎症反应甚至内毒素休克，但正常情况下机体并未产生肠道炎症及休克紊乱，肠道上皮细胞在其中扮演了重要角色，然而其究竟是怎样调控LPS介导的炎症反应并不清楚。我们研究发现肠道上皮细胞exosomes在抑制LPS诱导的炎症反应中起重要作用。LPS诱导的脓毒性休克小鼠模型中，肠道上皮细胞exosomes治疗组小鼠炎症反应明显减轻，生存期显著延长。体外实验表明，肠道上皮细胞exosomes干预组LPS刺激的巨噬细胞分泌产生的炎症细胞因子IL-6和TNF-a及巨噬细胞活化分子MHCII、CD86表达明显下降。本课题在前期实验基础上，从细胞、分子、动物模型、组织病理等不同层面，研究肠道上皮细胞exosomes在调控LPS诱导的炎症反应中的作用及其机制，同时为其将来可能作为一种新型药物用于临床控制和治疗LPS诱导的炎症反应提供理论基础和实验依据。

机体肠道内含有很多细菌并释放大量内毒素，这可能导致炎症反应甚至内毒素休克，但正常情况下机体并未产生肠道炎症及休克紊乱，肠道上皮细胞在其中扮演了重要角色，然而其究竟是怎样调控LPS介导的炎症反应并不清楚。我们研究发现肠道上皮细胞exosomes在抑制LPS诱导的炎症反应中起重要作用。LPS诱导的脓毒性休克小鼠模型中，肠道上皮细胞exosomes治疗组小鼠炎症反应明显减轻，生存期显著延长。体外实验表明，肠道上皮细胞exosomes干预组LPS刺激的巨噬细胞分泌产生的炎症细胞因子IL-6和TNF-a及巨噬细胞活化分子MHCII、CD86表达明显下降。本课题在前期实验基础上，从细胞、分子、动物模型、组织病理等不同层面，研究肠道上皮细胞exosomes在调控LPS诱导的炎症反应中的作用及其机制，同时为其将来可能作为一种新型药物用于临床控制和治疗LPS诱导的炎症反应提供理论基础和实验依据。