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提取物可预防脂多糖和棕榈酸诱导的促炎细胞因子产生和炎症小体形成。

extract protects against lipopolysaccharide and palmitate-induced production of proinflammatory cytokines and inflammasome formation.

机构信息

Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea.

Research Institute of Human Ecology, Korea University, Seoul 02841, Republic of Korea.

出版信息

Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11845. Epub 2021 Jan 26.

Abstract

Inflammation and the inflammasome complex formation are associated with numerous diseases, and palmitates or lipopolysaccharides (LPS) have been identified as potential links between these disorders. Recently, edible insects such as the  (GB) and the larva of have emerged as alternative food sources. In the present study, the effect of GB on LPS‑ or palmitate‑induced production of inflammatory cytokines, the formation of the inflammasome complex, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress and cell death was investigated in RAW264.7 cells. The results revealed that GB extract downregulated the production of inflammatory cytokines (such as TNF‑α, IL‑1β and IL‑6). Since the role of the MAP kinase and NF‑κB signalling pathways in the production of inflammatory cytokines is well established, the translocation of p65 into the nucleus and the phosphorylation of IκB and MAP kinases were further examined. Both these processes were upregulated following LPS and palmitate treatment, but they were inhibited by the GB extract. Moreover, GB extract decreased LPS/palmitate‑induced inflammasome complex formation (assessed via analysing the levels of the apoptosis‑associated speck‑like protein containing a caspase‑recruitment domain, NOD‑like receptor family pyrin domain containing 3, cleaved caspase‑1 and IL‑1β), the generation of ROS, ER stress and cell death. Treatment with SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor) and pyrrolidinedithiocarbamate ammonium (an NF‑κB inhibitor) decreased the production of inflammatory cytokines, as well as helped in the recovery of LPS/palmitate‑induced cell death. Overall, GB extract served an inhibitory role in LPS/palmitate‑induced inflammation via inhibiting the MAP kinase and NF‑κB signalling pathways, inflammasome complex formation, ROS generation, ER stress and cell death.

摘要

炎症和炎性小体复合物的形成与许多疾病有关,已鉴定出棕榈酸盐或脂多糖(LPS)是这些疾病之间的潜在联系。最近,诸如(GB)和的幼虫等食用昆虫已成为替代食物来源。在本研究中,研究了 GB 对 LPS 或棕榈酸盐诱导的炎症细胞因子产生、炎性小体复合物形成、活性氧(ROS)生成、内质网(ER)应激和细胞死亡的影响 RAW264.7 细胞。结果表明,GB 提取物下调了炎症细胞因子(如 TNF-α、IL-1β和 IL-6)的产生。由于 MAP 激酶和 NF-κB 信号通路在炎症细胞因子产生中的作用已得到充分证实,因此进一步检查了 p65 向核内易位和 IκB 和 MAP 激酶的磷酸化。这两个过程在 LPS 和棕榈酸盐处理后均被上调,但被 GB 提取物抑制。此外,GB 提取物降低了 LPS/棕榈酸盐诱导的炎性小体复合物形成(通过分析凋亡相关斑点样蛋白,含有半胱氨酸天冬氨酸蛋白酶募集域,NOD 样受体家族含有吡咯烷域 3,切割的半胱氨酸天冬氨酸蛋白酶-1 和 IL-1β 的水平)、ROS 的产生、ER 应激和细胞死亡。用 SB203580(p38 抑制剂)、SP600125(JNK 抑制剂)和吡咯烷二硫代氨基甲酸盐铵(NF-κB 抑制剂)处理可减少炎症细胞因子的产生,并有助于恢复 LPS/棕榈酸盐诱导的细胞死亡。总体而言,GB 提取物通过抑制 MAP 激酶和 NF-κB 信号通路、炎性小体复合物形成、ROS 生成、ER 应激和细胞死亡,在 LPS/棕榈酸盐诱导的炎症中发挥抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e4/7821350/1ba95db41719/mmr-23-03-11845-g00.jpg

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