Hot-water extract of ripened Pu-erh tea attenuates DSS-induced colitis through modulation of the NF-κB and HIF-1α signaling pathways in mice.
熟化普洱茶热水提取物通过调节小鼠 NF-κ b 和 hif-1 α 信号通路减轻 DSS 诱导的结肠炎。
- 作者列表："Huang Y","Qiu L","Mi X","Zhang Z","Xu D","Tao X","Xing K","Wu Q","Wei H
:Tea consumption has been found to be associated with low incidence of inflammatory bowel disease in Asian countries. However, there is very limited knowledge of such potential protection and its underlying mechanism. Ripened Pu-erh tea (RPT) belongs to the variety of microbial fermented tea, but its function regarding anti-inflammation remains unclear. In the present study, we investigated the effects of RPT on dextran sulfate sodium (DSS)-induced colitis in mice. The results demonstrated that RPT significantly relieved the loss of body weight, disease severity and shortening of colon length, and remarkably inhibited the secretion of pro-inflammatory cytokines by lessening the infiltration of inflammatory cells. Furthermore, we found that RPT suppressed the activation of the NF-κB pathway and down-regulated the expression of HIF-1α. Thus, it was concluded that RPT attenuated the progress of colitis via suppressing the HIF-1α/NF-κB signaling pathways thus reducing inflammation. This suggests that RPT may be a potential anti-inflammatory nutraceutical for the prevention and treatment of colonic colitis.
: 在亚洲国家，已发现茶叶消费与炎症性肠病的低发病率相关。然而，对这种潜在保护及其潜在机制的了解非常有限。成熟普洱茶 (RPT) 属于微生物发酵茶的品种，但其抗炎作用尚不清楚。在本研究中，我们研究了 RPT 对葡聚糖硫酸钠 (DSS) 诱导的小鼠结肠炎的影响。结果表明，RPT 能明显减轻体重下降、疾病严重程度和结肠长度缩短，并能明显抑制炎性细胞因子的分泌，减少炎性细胞浸润。此外，我们发现 RPT 抑制 NF-κ b 通路的激活，下调 hif-1 α 的表达。由此得出结论，RPT 通过抑制 hif-1 α/NF-κ b 信号通路从而减轻炎症，从而减轻结肠炎的进展。这表明 RPT 可能是一种潜在的预防和治疗结肠炎的抗炎营养药。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.