Journal of thoracic disease · 2024
Ethyl palmitate ameliorates lethal endotoxemia by inducing hepatic fetuin-A secretion: an in vivo and in vitro experiment.
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Chen Guannan, Song Jieqiong, Zhou Yue, Wu Yuanyuan, Yang Chenghang, Wang Yingqin, Zhong Ming
Аннотация
BACKGROUND: Ethyl palmitate (EP) is known to promote hepatic fetuin-A production and modulate inflammatory responses, but its potential role in lethal endotoxemia and sepsis remains unclear. This study investigates the plasma fetuin-A levels and further evaluates the impact of hepatic fetuin-A induced by EP on systemic inflammation and macrophage polarization in lethal endotoxemia and sepsis.
METHODS: Blood samples from 55 sepsis patients and 18 non-septic controls with similar age and sex ratio were collected to perform proteomic analyses and identify significantly different proteins. Serum fetuin-A levels in lipopolysaccharide (LPS) induced endotoxemia mice were assayed by enzyme-linked immunosorbent assay (ELISA). The mouse hepatocyte cell (AML-12) was exposed to different concentrations of EP. In vivo experiments were conducted in which adult male C57BL/6J mice were given EP with or without intraperitoneal LPS. Fetuin-A was determined via western blot and immunohistochemical staining. Survival rates, lung and liver injury and levels of pro-inflammatory cytokines were also monitored and assessed using histology, real-time quantitative polymerase chain reaction (RT-qPCR) and ELISA. Additionally, the proportion of macrophages and M1/M2 subtypes in the lung and liver tissues were evaluated by flow cytometry.
RESULTS: Our proteomic results revealed that the plasma fetuin-A levels were significantly decreased in sepsis patients compared with non-septic controls. Similarly, the serum fetuin-A levels were also reduced in endotoxemia mice compared with the control group. EP effectively promoted the production of fetuin-A in AML-12 cells and murine liver tissues. Subsequently, activation of fetuin-A by EP dramatically reduced LPS-induced murine mortality, alleviated lung and liver injury, down-regulated pro-inflammatory mediators and macrophage infiltration. Furthermore, EP regulated macrophage polarization from the M1 (CD45+CD11b+F4/80+CD86+) to the M2 (CD45+CD11b+F4/80+CD206+) subtype in murine liver tissue.
CONCLUSIONS: EP-induced production of fetuin-A prevents sepsis and endotoxemia progression by promoting M2 polarization of macrophages.
METHODS: Blood samples from 55 sepsis patients and 18 non-septic controls with similar age and sex ratio were collected to perform proteomic analyses and identify significantly different proteins. Serum fetuin-A levels in lipopolysaccharide (LPS) induced endotoxemia mice were assayed by enzyme-linked immunosorbent assay (ELISA). The mouse hepatocyte cell (AML-12) was exposed to different concentrations of EP. In vivo experiments were conducted in which adult male C57BL/6J mice were given EP with or without intraperitoneal LPS. Fetuin-A was determined via western blot and immunohistochemical staining. Survival rates, lung and liver injury and levels of pro-inflammatory cytokines were also monitored and assessed using histology, real-time quantitative polymerase chain reaction (RT-qPCR) and ELISA. Additionally, the proportion of macrophages and M1/M2 subtypes in the lung and liver tissues were evaluated by flow cytometry.
RESULTS: Our proteomic results revealed that the plasma fetuin-A levels were significantly decreased in sepsis patients compared with non-septic controls. Similarly, the serum fetuin-A levels were also reduced in endotoxemia mice compared with the control group. EP effectively promoted the production of fetuin-A in AML-12 cells and murine liver tissues. Subsequently, activation of fetuin-A by EP dramatically reduced LPS-induced murine mortality, alleviated lung and liver injury, down-regulated pro-inflammatory mediators and macrophage infiltration. Furthermore, EP regulated macrophage polarization from the M1 (CD45+CD11b+F4/80+CD86+) to the M2 (CD45+CD11b+F4/80+CD206+) subtype in murine liver tissue.
CONCLUSIONS: EP-induced production of fetuin-A prevents sepsis and endotoxemia progression by promoting M2 polarization of macrophages.