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Published on: November 23, 2017
Effects of platelet-activating factor, tumor necrosis factor, and interleukin-1alpha on the expression of
Ning Xu1, Xiao-Ying Zhang, Xuan Dong
1Department of Clinical Chemistry, University Hospital of Lund, Lund, S-221 85, Sweden. ning.xu@klinkem.lu.se
Abstract:
Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL) in plasma, exclusively expressed in liver and in kidney. The function of apoM is yet unknown. The human apoM gene is located in the major histocompatibility complex class III region on chromosome 6. Because many genes located in this region are related to the immune response, we have investigated whether apoM might also be involved in the host inflammatory response. In this study we examined effects of the platelet-activating factor (PAF), tumor necrosis factor (TNF-alpha), and interleukin-1alpha (IL-1alpha) on apoM expression in a hepatoblastoma cell line, HepG2 cells. PAF significantly enhanced the apoM mRNA levels and the secretion of apoM in HepG2 cell cultures. The enhancement of apoM secretion is seen at a low concentration of PAF (2 ng/ml), whereas a high concentration of PAF increases both the apoM mRNA levels and apoM secretion. Neither TNF-alpha nor IL-1alpha influenced apoM mRNA level and secretion. Furthermore, Lexipafant, a PAF-receptor (PAF-R) antagonist significantly suppressed the mRNA level and the secretion of apoM in HepG2 cells in a dose-dependent manner. Neither PAF nor Lexipafant influenced the mRNA levels and the secretion of apoA-I, apoB and apoE in HepG2 cells, indicating that the effects of PAF or Lexipafant on the apoM production on hepatic cells are selective for apoM. The cellular mechanism of the effects of PAF or Lexipafant on apoM metabolism requires further investigations.
Insights
Platelet-activating factor (PAF) significantly increases apolipoprotein M (apoM) production in liver cells. This suggests apoM may play a role in the inflammatory response, as its production is selectively modulated by PAF signaling.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Apolipoprotein M (apoM) is a plasma protein found in high-density lipoprotein (HDL), primarily expressed in the liver and kidneys.
- The precise function of apoM remains largely unknown.
- The apoM gene's location within the major histocompatibility complex class III region suggests a potential role in immune responses.
Purpose of the Study:
- To investigate the potential involvement of apolipoprotein M (apoM) in the host inflammatory response.
- To examine the effects of key inflammatory mediators, including platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1alpha (IL-1alpha), on apoM expression in hepatic cells.
Main Methods:
- Utilized HepG2 cells, a human hepatoblastoma cell line, to model hepatic apoM expression.
- Assessed the impact of PAF, TNF-alpha, and IL-1alpha on apoM mRNA levels and apoM secretion.
- Investigated the effect of Lexipafant, a specific PAF-receptor antagonist, on apoM production and secretion.
Main Results:
- Platelet-activating factor (PAF) significantly enhanced both apoM mRNA levels and apoM secretion in HepG2 cells in a dose-dependent manner.
- Neither TNF-alpha nor IL-1alpha demonstrated any significant effect on apoM mRNA or secretion.
- Lexipafant, a PAF-receptor antagonist, dose-dependently suppressed apoM mRNA levels and secretion, indicating a selective effect on apoM production.
Conclusions:
- Platelet-activating factor (PAF) selectively upregulates apolipoprotein M (apoM) expression and secretion in hepatic cells.
- The findings suggest a potential role for apoM in the inflammatory response mediated by PAF signaling.
- Further research is warranted to elucidate the specific cellular mechanisms underlying PAF's influence on apoM metabolism.
