Inhibition of STAT3 phosphorylation by colchicine regulates NLRP3 activation to alleviate sepsis-induced acute lung injury
Abstract The pharmacotherapeutic mechanism of colchicine, a tricyclic, lipid-soluble alkaloid extracted from the plant of the Lily family Colchicum autumnale, has not been fully understood in diverse disorders, including sepsis-induced acute lung injury (ALI). The study aimed at exploring the impact of colchicine on sepsis-induced ALI and the relevant mechanisms. Colchicine significantly attenuated ALI in mice caused by sepsis by alleviating respiratory dysfunction and pulmonary edema in mice, inhibiting NLRP3 inflammasome formation, and reducing oxidative stress, pyroptosis, and apoptosis of murine alveolar macrophage (J774A.1) cells. The targets of colchicine were predicted in the superPRED database and intersected with the differentially expressed genes in the GSE5883 and GSE129775 datasets. The major targets were subjected to protein–protein interaction network generation and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. It was thus found that colchicine inhibited STAT3 phosphorylation but did not alter STAT3 total protein expression. Phosphorylated STAT3 recruited EP300 to form a complex to promote histone H3 acetylation and histone H4 acetylation of NLRP3 promoter, leading to pyroptosis of J774A.1 cells. In conclusion, inhibition of STAT3 phosphorylation by colchicine represses NLRP3 promoter acetylation via the STAT3/EP300 complex, thereby alleviating ALI caused by sepsis..
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
|---|---|
| Enthalten in: |
Inflammopharmacology - 31(2023), 4 vom: 28. Apr., Seite 2007-2021 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Yuanshui [VerfasserIn] |
|---|
| Links: |
Volltext [lizenzpflichtig] |
|---|
| BKL: | |
|---|---|
| Themen: |
| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
|---|
| doi: |
10.1007/s10787-023-01199-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC2144505411 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | OLC2144505411 | ||
| 003 | DE-627 | ||
| 005 | 20240118095428.0 | ||
| 007 | tu | ||
| 008 | 240118s2023 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s10787-023-01199-9 |2 doi | |
| 035 | |a (DE-627)OLC2144505411 | ||
| 035 | |a (DE-He213)s10787-023-01199-9-p | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a 44.00 |2 bkl | ||
| 100 | 1 | |a Liu, Yuanshui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhibition of STAT3 phosphorylation by colchicine regulates NLRP3 activation to alleviate sepsis-induced acute lung injury |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. | ||
| 520 | |a Abstract The pharmacotherapeutic mechanism of colchicine, a tricyclic, lipid-soluble alkaloid extracted from the plant of the Lily family Colchicum autumnale, has not been fully understood in diverse disorders, including sepsis-induced acute lung injury (ALI). The study aimed at exploring the impact of colchicine on sepsis-induced ALI and the relevant mechanisms. Colchicine significantly attenuated ALI in mice caused by sepsis by alleviating respiratory dysfunction and pulmonary edema in mice, inhibiting NLRP3 inflammasome formation, and reducing oxidative stress, pyroptosis, and apoptosis of murine alveolar macrophage (J774A.1) cells. The targets of colchicine were predicted in the superPRED database and intersected with the differentially expressed genes in the GSE5883 and GSE129775 datasets. The major targets were subjected to protein–protein interaction network generation and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. It was thus found that colchicine inhibited STAT3 phosphorylation but did not alter STAT3 total protein expression. Phosphorylated STAT3 recruited EP300 to form a complex to promote histone H3 acetylation and histone H4 acetylation of NLRP3 promoter, leading to pyroptosis of J774A.1 cells. In conclusion, inhibition of STAT3 phosphorylation by colchicine represses NLRP3 promoter acetylation via the STAT3/EP300 complex, thereby alleviating ALI caused by sepsis. | ||
| 650 | 4 | |a Colchicine | |
| 650 | 4 | |a STAT3 | |
| 650 | 4 | |a NLRP3 | |
| 650 | 4 | |a EP300 | |
| 650 | 4 | |a Sepsis-induced acute lung injury | |
| 700 | 1 | |a Yang, Hang |4 aut | |
| 700 | 1 | |a Zhu, Fei |4 aut | |
| 700 | 1 | |a Ouyang, Yanhong |4 aut | |
| 700 | 1 | |a Pan, Pinhua |0 (orcid)0000-0001-5883-0531 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Inflammopharmacology |d Springer International Publishing, 1991 |g 31(2023), 4 vom: 28. Apr., Seite 2007-2021 |w (DE-627)170602893 |w (DE-600)1080058-X |w (DE-576)505034115 |x 0925-4692 |7 nnns |
| 773 | 1 | 8 | |g volume:31 |g year:2023 |g number:4 |g day:28 |g month:04 |g pages:2007-2021 |
| 856 | 4 | 1 | |u https://doi.org/10.1007/s10787-023-01199-9 |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a GBV_ILN_4277 | ||
| 936 | b | k | |a 44.00 |q VZ |
| 951 | |a AR | ||
| 952 | |d 31 |j 2023 |e 4 |b 28 |c 04 |h 2007-2021 | ||