Angiotensin II type 2 receptor agonist attenuates LPS-induced acute lung injury through modulating THP-1-derived macrophage reprogramming
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
Acute respiratory distress syndrome (ARDS) is a devastating respiratory disorder, characterized by overwhelming inflammation in the alveoli without effective pharmacological treatment. We aimed to investigate the effect and mechanism of angiotensin II type 2 receptor (AT2R) agonist, Compound 21 (C21), on the lipopolysaccharide (LPS)-induced acute lung injury (ALI) model. The protective effect of C21 was evaluated via enzyme-linked immunosorbent assay (ELISA), Western blot (WB), real-time PCR, and fluorescence microscopy in LPS-challenged THP1-derived macrophages. Besides, the in vivo efficacy of C21 was assessed using cell counting, ELISA, protein quantification, hematoxylin-eosin (H&E) staining, and WB in an LPS-induced ALI mouse model. The results showed that C21 significantly inhibited the secretion of pro-inflammatory cytokines (CCL-2, IL-6), overproduction of intracellular ROS, and activation of inflammatory pathways (NF-κB/NLRP3, p38/MAPK) in THP-1 cell-derived macrophages stimulated by LPS. In in vivo study, intraperitoneal injection of C21 could reduce airway leukocytes accumulation and chemokine/cytokine (keratinocyte chemoattractant (KC), IL-6) generation, as well as alleviate diffuse alveolar damage induced by LPS. Conclusively, the AT2R agonist C21 significantly inhibited LPS-stimulated excess inflammatory responses and oxidative stress in macrophages. Meanwhile, C21 could effectively alleviate acute inflammation and tissue damage in the lungs of ALI mice challenged by LPS. The results of this study bring new hope for the early treatment of ALI/ARDS.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:397 |
---|---|
Enthalten in: |
Naunyn-Schmiedeberg's archives of pharmacology - 397(2024), 1 vom: 18. Jan., Seite 99-108 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Chen, Liangzhi [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 08.01.2024 Date Revised 19.01.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1007/s00210-023-02589-0 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM358693829 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM358693829 | ||
003 | DE-627 | ||
005 | 20240119231843.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s00210-023-02589-0 |2 doi | |
028 | 5 | 2 | |a pubmed24n1264.xml |
035 | |a (DE-627)NLM358693829 | ||
035 | |a (NLM)37368029 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Chen, Liangzhi |e verfasserin |4 aut | |
245 | 1 | 0 | |a Angiotensin II type 2 receptor agonist attenuates LPS-induced acute lung injury through modulating THP-1-derived macrophage reprogramming |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 08.01.2024 | ||
500 | |a Date Revised 19.01.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
520 | |a Acute respiratory distress syndrome (ARDS) is a devastating respiratory disorder, characterized by overwhelming inflammation in the alveoli without effective pharmacological treatment. We aimed to investigate the effect and mechanism of angiotensin II type 2 receptor (AT2R) agonist, Compound 21 (C21), on the lipopolysaccharide (LPS)-induced acute lung injury (ALI) model. The protective effect of C21 was evaluated via enzyme-linked immunosorbent assay (ELISA), Western blot (WB), real-time PCR, and fluorescence microscopy in LPS-challenged THP1-derived macrophages. Besides, the in vivo efficacy of C21 was assessed using cell counting, ELISA, protein quantification, hematoxylin-eosin (H&E) staining, and WB in an LPS-induced ALI mouse model. The results showed that C21 significantly inhibited the secretion of pro-inflammatory cytokines (CCL-2, IL-6), overproduction of intracellular ROS, and activation of inflammatory pathways (NF-κB/NLRP3, p38/MAPK) in THP-1 cell-derived macrophages stimulated by LPS. In in vivo study, intraperitoneal injection of C21 could reduce airway leukocytes accumulation and chemokine/cytokine (keratinocyte chemoattractant (KC), IL-6) generation, as well as alleviate diffuse alveolar damage induced by LPS. Conclusively, the AT2R agonist C21 significantly inhibited LPS-stimulated excess inflammatory responses and oxidative stress in macrophages. Meanwhile, C21 could effectively alleviate acute inflammation and tissue damage in the lungs of ALI mice challenged by LPS. The results of this study bring new hope for the early treatment of ALI/ARDS | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Acute lung injury | |
650 | 4 | |a Angiotensin II type2 receptor agonist | |
650 | 4 | |a C21 | |
650 | 4 | |a Inflammation | |
650 | 4 | |a Macrophage | |
650 | 7 | |a compound 21 |2 NLM | |
650 | 7 | |a RC2V4W0EYC |2 NLM | |
650 | 7 | |a Lipopolysaccharides |2 NLM | |
650 | 7 | |a Receptor, Angiotensin, Type 2 |2 NLM | |
650 | 7 | |a Interleukin-6 |2 NLM | |
650 | 7 | |a Cytokines |2 NLM | |
650 | 7 | |a NF-kappa B |2 NLM | |
700 | 1 | |a Gong, Ping |e verfasserin |4 aut | |
700 | 1 | |a Su, Yue |e verfasserin |4 aut | |
700 | 1 | |a Meng, Linlin |e verfasserin |4 aut | |
700 | 1 | |a Wang, Muyun |e verfasserin |4 aut | |
700 | 1 | |a Gao, Wei |e verfasserin |4 aut | |
700 | 1 | |a Liu, Qinghua |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Naunyn-Schmiedeberg's archives of pharmacology |d 1972 |g 397(2024), 1 vom: 18. Jan., Seite 99-108 |w (DE-627)NLM000008354 |x 1432-1912 |7 nnns |
773 | 1 | 8 | |g volume:397 |g year:2024 |g number:1 |g day:18 |g month:01 |g pages:99-108 |
856 | 4 | 0 | |u http://dx.doi.org/10.1007/s00210-023-02589-0 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 397 |j 2024 |e 1 |b 18 |c 01 |h 99-108 |