L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), o...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2023-10-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100673&tlng=en |
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| author | Dandan Wu Haiyan He Jinliang Chen Sumei Yao Haiqin Xie Wenyan Jiang Xuedong Lv Wei Gao Linlin Meng Xin Yao |
| author_facet | Dandan Wu Haiyan He Jinliang Chen Sumei Yao Haiqin Xie Wenyan Jiang Xuedong Lv Wei Gao Linlin Meng Xin Yao |
| author_sort | Dandan Wu |
| collection | DOAJ |
| description | Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome. |
| first_indexed | 2024-03-11T16:30:26Z |
| format | Article |
| id | doaj.art-abd530afb249478481742c6678b4d0b2 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-03-11T16:30:26Z |
| publishDate | 2023-10-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-abd530afb249478481742c6678b4d0b22023-10-24T07:38:19ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2023-10-015610.1590/1414-431x2023e12830L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophagesDandan Wuhttps://orcid.org/0000-0003-2479-2703Haiyan Hehttps://orcid.org/0009-0004-2846-2124Jinliang Chenhttps://orcid.org/0000-0003-2788-1226Sumei Yaohttps://orcid.org/0009-0008-9021-6724Haiqin Xiehttps://orcid.org/0000-0002-9109-1299Wenyan Jianghttps://orcid.org/0009-0000-1339-529XXuedong Lvhttps://orcid.org/0009-0000-8337-9412Wei Gaohttps://orcid.org/0000-0003-1026-3878Linlin Menghttps://orcid.org/0000-0002-9080-6571Xin Yaohttps://orcid.org/0000-0002-1301-3631Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100673&tlng=enAcute lung injuryMacrophagesL-carnitineLipid accumulationAnti-inflammation |
| spellingShingle | Dandan Wu Haiyan He Jinliang Chen Sumei Yao Haiqin Xie Wenyan Jiang Xuedong Lv Wei Gao Linlin Meng Xin Yao L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages Brazilian Journal of Medical and Biological Research Acute lung injury Macrophages L-carnitine Lipid accumulation Anti-inflammation |
| title | L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages |
| title_full | L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages |
| title_fullStr | L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages |
| title_full_unstemmed | L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages |
| title_short | L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages |
| title_sort | l carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages |
| topic | Acute lung injury Macrophages L-carnitine Lipid accumulation Anti-inflammation |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100673&tlng=en |
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