Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS.
Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS.
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苯丙氨酸通过激活CaSR促进ARDS时肺泡巨噬细胞焦亡
DOI：
10.3389/fimmu.2023.1114129
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发表时间：
2023
影响因子：
7.3
通讯作者：
Liu, Jialin
中科院分区：
文献类型：
--
作者：
Tang, Yiding;Yu, Yue;Li, Ranran;Tao, Zheying;Zhang, Li;Wang, Xiaoli;Qi, Xiaoling;Li, Yinjiaozhi;Meng, Tianjiao;Qu, Hongping;Zhou, Mi;Xu, Jing;Liu, Jialin
急性呼吸窘迫综合征（ARDS）与重症监护病房（ICU）患者的高死亡率相关，这些患者被认为是内因的压倒性炎症。作者之前的研究表明苯丙氨酸水平与肺损伤之间存在潜在的相关性。苯丙氨酸通过增强先天免疫反应和促炎细胞因子的释放诱导炎症。肺泡巨噬细胞（AMs）通过焦亡反应炎症介质的合成和释放，焦亡是一种程序性细胞死亡形式，通过核苷酸结合寡聚化结构域样受体蛋白3 （NLRP3）信号通路，导致caspase-1和gasdermin D （GSDMD）的分裂和白细胞介素(IL) -1β和IL-18的释放，加重ARDS患者的肺部炎症和损伤。在本研究中，苯丙氨酸促进了AMs的焦亡，从而加重了小鼠的肺部炎症和ARDS的致死率。此外，苯丙氨酸通过激活钙敏感受体（CaSR）启动NLRP3通路。这些发现揭示了苯丙氨酸在ARDS中的关键作用机制，并可能成为ARDS的新治疗靶点。
Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming inflammation considered to be an internal cause. The authors’ previous study indicated a potential correlation between phenylalanine levels and lung injury. Phenylalanine induces inflammation by enhancing the innate immune response and the release of pro-inflammatory cytokines. Alveolar macrophages (AMs) can respond to stimuli via synthesis and release of inflammatory mediators through pyroptosis, one form of programmed cell death acting through the nucleotide-binging oligomerization domain-like receptors protein 3 (NLRP3) signaling pathway, resulting in the cleavage of caspase-1 and gasdermin D (GSDMD) and the release of interleukin (IL) -1β and IL-18, aggravating lung inflammation and injury in ARDS. In this study, phenylalanine promoted pyroptosis of AMs, which exacerbated lung inflammation and ARDS lethality in mice. Furthermore, phenylalanine initiated the NLRP3 pathway by activating the calcium-sensing receptor (CaSR). These findings uncovered a critical mechanism of action of phenylalanine in the context of ARDS and may be a new treatment target for ARDS.
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影响因子：
5.6
作者：
Luporini RL;Pott-Junior H;Di Medeiros Leal MCB;Castro A;Ferreira AG;Cominetti MR;de Freitas Anibal F
通讯作者：
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影响因子：
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24.3
作者：
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通讯作者：
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