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首页> 外文期刊>American Journal of Physiology >Protective effects of guggulsterone against colitis are associated with the suppression of TREM-1 and modulation of macrophages
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Protective effects of guggulsterone against colitis are associated with the suppression of TREM-1 and modulation of macrophages

机译：Guggulsterons对结肠炎的保护作用与抑制Trem-1和巨噬细胞的调节相关

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Triggering receptor expressed on myeloid cells 1 (TREM-1)-expressing intestinal macrophages are significantly increased in the colons of patients with inflammatory bowel disease (IBD). We focused here on the effects of guggulsterone on macrophage modulation in colitis as a potential therapeutic molecule in human IBD and explore the underlying mechanisms. Gene expression in macrophages was examined and wound-healing assay using HT-29 cells was performed. Colitis in wild-type and IL-10-, Toll-like receptor 4 (TLR4)-, and myeloid differentiation primary response 88 (MyD88)-deficient mice was induced via the administration of 2, , -trinitrobenzene sulfonic acid (TNBS) into the colon. In both in vitro and in vivo experiments, guggulsterone suppressed intestinal inflammation amplified by TREM-1 stimulation, in which the suppression of NF-kB, activating protein-1, and proteasome pathways was involved. In the TNBS-induced colitis model, guggulsterone reduced disease activity index scores and TREM-1 expression, stimulated IL-10 production, and improved survival in wild-type mice. These effects were not observed in IL-10-, TLR4-, and MyD88-deficient mice. Guggulsterone also suppressed Ml polarization, yet induced the M2 phenotype in macrophages from IBD patients as well as from mice. These findings indicate that guggulsterone blocks the hy peracti vation of macrophages via TREM-1 suppression and induces M2 polarization via IL-10 mediated by the TLR4 signaling pathway. Furthermore, this study provides a new rationale for the therapeutic potential of guggulsterone in the treatment of IBD.
机译：在炎症性肠病患者（IBD）的患者的核心中显着增加，在骨髓细胞1（TREM-1）中表达的触发受体显着增加。我们专注于Guggulsterone对结肠炎巨噬细胞调节的影响，作为人体IBD中的潜在治疗分子，探索潜在机制。进行巨噬细胞中的基因表达，并进行使用HT-29细胞的伤口愈合测定。通过施用2，-Trinitrobenene磺酸（TNB）诱导野生型和IL-10-，Toll样受体4（TLR4） - 和骨髓分化初级响应88（MYD88） - 霉菌小鼠中的结肠炎结肠。在体外和体内实验中，Guggulsterone抑制了通过Trem-1刺激扩增的肠道炎症，其中涉及NF-Kb，活化蛋白-1和蛋白酶体途径的抑制。在TNBS诱导的结肠炎模型中，Guggulsterone降低了疾病活动指数评分和Trem-1表达，刺激了IL-10的生产，并在野生型小鼠中提高了存活。在IL-10-，TLR4和MyD88缺陷小鼠中未观察到这些效果。 Guggulsterone还抑制ML极化，但诱导来自IBD患者的巨噬细胞的M2表型以及小鼠。这些发现表明，Guggulsterone通过TRM-1抑制阻止巨噬细胞的Hy蠕动雌激酶，并通过由TLR4信号通路介导的IL-10诱导M2偏振。此外，本研究为古街杆菌治疗IBD的治疗潜力提供了新的基本原理。

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