原蛋白通过通过PAMP-MRGPRX2反循环调节乳腺细胞脱粒化来改善炎症性性结肠炎
Yihan Huang1, Na Wang2, Xiaolan Ji1
1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
概括
原蛋白 (API) 通过抑制巨细胞降粒和阻断炎症通路,有效治疗性结肠炎 (UC). 这种天然的黄类化合物通过向PAMP-MRGPRX2信号轴,为UC提供了一个有前途的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 性结肠炎 (UC) 的进展与涉及Mas相关G蛋白结合受体X2 (MRGPRX2) 和其配体PAMP-12的促炎反循环有关.
- 针对UC治疗的MRGPRX2的向仍未得到充分研究,尽管自然化合物如阿皮基宁 (API) 的抗炎作用潜力较小.
研究的目的:
- 研究阿皮基宁 (API) 对性结肠炎 (UC) 的治疗作用.
- 通过调节PAMP-MRGPRX2-介导的瘤细胞 (MC) 脱粒的机制来阐明API的作用机制.
主要方法:
- 研究人员采用了一种硫酸 (DSS) 诱导的UC小鼠模型.
- 评估包括动物行为,血清学分析,组织学分析,mRNA测序,PCR,ELISA和野外类型和MC MrgprB2-条件淘汰赛小鼠的西部斑点.
- 用PAMP-12触发的MC脱粒的体外和体外模型来研究API的机制.
主要成果:
- 通过MrgprB2进行乳腺细胞 (MC) 降粒是持续性结肠炎炎症的关键.
- API减轻了结肠组织损伤,壮和髓氧化酶活性,同时改善了密室结构并减少了炎症细胞透.
- API抑制了MC降粒和碳氧酶A3 (CPA3) 水平,破坏了PAMP-MrgprB2的促炎反循环,并通过Akt1/XBP-1S/CHOP/TXNIP和NF-κB/IL-1β通路抑制了PAMP-12触发的MC降粒.
结论:
- 原蛋白 (API) 可以缓解UC炎症症状.
- 通过抑制PAMP-MRGPRX2 / B2介导的持续MC降粒反循环,API的作用.
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