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Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS

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 lev...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291621/
https://www.ncbi.nlm.nih.gov/pubmed/37377971
http://dx.doi.org/10.3389/fimmu.2023.1114129
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author 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
author_facet 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
author_sort Tang, Yiding
collection PubMed
description 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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spelling pubmed-102916212023-06-27 Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS 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 Front Immunol Immunology 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. Frontiers Media S.A. 2023-06-12 /pmc/articles/PMC10291621/ /pubmed/37377971 http://dx.doi.org/10.3389/fimmu.2023.1114129 Text en Copyright © 2023 Tang, Yu, Li, Tao, Zhang, Wang, Qi, Li, Meng, Qu, Zhou, Xu and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
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
Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS
title Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS
title_full Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS
title_fullStr Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS
title_full_unstemmed Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS
title_short Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS
title_sort phenylalanine promotes alveolar macrophage pyroptosis via the activation of casr in ards
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291621/
https://www.ncbi.nlm.nih.gov/pubmed/37377971
http://dx.doi.org/10.3389/fimmu.2023.1114129
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