Effect of dodecanoylcarnitine and myristoleic acid on the cellular function of mouse alveolar epithelial cell line of MLE-12
10.3969/j.issn.1672-8467.2025.03.003
- VernacularTitle:十二烷酰肉碱和肉豆蔻酸对小鼠肺泡上皮细胞系MLE-12细胞功能的影响
- Author:
Yuan MA
1
;
Ting ZHANG
;
Zhi-long JIANG
;
Jia-meng GAO
;
Yu-hao QIAN
;
Zhi-hong CHEN
Author Information
1. 复旦大学附属中山医院呼吸与危重医学科 上海 200032
- Publication Type:Journal Article
- Keywords:
asthma;
metabolism;
dodecanoylcarnitine(DA);
myristoleic acid(MA);
JTE-013;
mouse
- From:
Fudan University Journal of Medical Sciences
2025;52(3):333-342
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of dodecanoylcarnitine(DA)and myristoleic acid(MA)on the function of mouse alveolar epithelial cell line MLE-12 and their underlying mechanisms.Methods An inflammatory model was established by stimulating MLE-12 cells with IL-4.The expression levels of DA,MA,and sphingosine-1-phosphate(S1P)in the cell supernatant were detected by ELISA.MLE-12 cells were separately intervened with DA and MA.RT-PCR and flow cytometry were used to detect the expression changes of inflammatory factors IL-6 and tumor necrosis factor-α(TNF-α)and the level of intracellular reactive oxygen species(ROS).Additionally,Western blot was performed to detect the expression of key proteins such as p38 mitogen-activated protein kinase(p-38 MAPK)and src homology 2 domain-containing phosphatase 1(SHP-1).To explore the role of S1PR2 in the effects of DA and MA,MLE-12 cells were pretreated with the S1PR2 inhibitor JTE-013,and the above experiments were repeated.Results IL-4 stimulation significantly upregulated the levels of DA,MA,and S1P in MLE-12 cells(P<0.05).DA/MA treatment groups exhibited significantly increased expression of IL-6 and TNF-α compared with the control group(P<0.05),along with elevated ROS levels(P<0.05).Western blot analysis revealed that DA/MA promoted SHP-1 dephosphorylation and phosphorylated p38 MAPK activation in MLE-12 cells.Notably,JTE-013 pre-treatment completely reversed these effects(P<0.05).Conclusion Asthma-related metabolites DA and MA exacerbate the inflammatory and oxidative stress responses of MLE-12 cells by activating the S1PR2 receptor,promoting the dephosphorylation of SHP-1 and the activation of the p-p38 MAPK pathway.This study reveals the core regulatory role of S1PR2 in this pathway as well.
