Seo Dong-Won, Cho Yong-Il, Gu Suna, Kim Da-Hee, Yi Young-Joo, Lee Sang-Myeong
Gyeongbuk Institute for Bio industry, Andong-si, Gyeongbuk 760-380, South Korea.
Department of Animal Science and Technology, Suncheon National University, 255 Jungang-ro, Suncheon-si, Jeollanam-do 57922, South Korea.
Microbiol Immunol. 2018 Jan;62(1):44-54. doi: 10.1111/1348-0421.12557.
The inflammasome is a multiprotein signaling complex that mediates inflammatory innate immune responses through caspase 1 activation and subsequent IL-1β secretion. However, because its aberrant activation often leads to inflammatory diseases, targeting the inflammasome holds promise for the treatment of inflammation-related diseases. In this study, it was found that a hot-water extract of Sanguisorba officinalis (HSO) suppresses inflammasome activation triggered by adenosine 5'-triphosphate, nigericin, microbial pathogens, and double stranded DNA in bone marrow-derived macrophages. HSO was found to significantly suppress IL-1β production in a dose-dependent manner; this effect correlated well with small amounts of caspase 1 and little ASC pyroptosome formation in HSO-treated cells. The anti-inflammatory activity of HSO was further confirmed in a mouse model of endotoxin-induced septic shock. Oral administration of HSO reduced IL-1β titers in the serum and peritoneal cavity, increasing the survival rate. Taken together, our results suggest that HSO is an inhibits inflammasome activation through nucleotide-binding domain and leucine-rich repeat pyrin domain 3, nucleotide-binding domain and leucine-rich repeat caspase recruitment domain 4 and absent in melanoma 2 pathways, and may be useful for treatment of inflammasome-mediated diseases.
炎性小体是一种多蛋白信号复合体，通过半胱天冬酶1激活及随后的白细胞介素-1β分泌介导炎症性固有免疫反应。然而，由于其异常激活常导致炎症性疾病，靶向炎性小体有望用于治疗炎症相关疾病。在本研究中，发现地榆热水提取物（HSO）可抑制骨髓来源巨噬细胞中由三磷酸腺苷、尼日利亚菌素、微生物病原体和双链DNA触发的炎性小体激活。发现HSO以剂量依赖性方式显著抑制白细胞介素-1β的产生；这种作用与HSO处理的细胞中少量的半胱天冬酶1和少量的凋亡相关斑点样蛋白（ASC）焦亡小体形成密切相关。HSO的抗炎活性在内毒素诱导的脓毒症休克小鼠模型中得到进一步证实。口服HSO可降低血清和腹腔中的白细胞介素-1β滴度，提高存活率。综上所述，我们的结果表明，HSO通过核苷酸结合寡聚化结构域样受体蛋白3、核苷酸结合寡聚化结构域样受体蛋白4和黑色素瘤缺乏因子2途径抑制炎性小体激活，可能对治疗炎性小体介导的疾病有用。
