Regular Article
Effects of Platelet-Activating Factor, Tumor Necrosis Factor, and Interleukin-1α on the Expression of Apolipoprotein M in HepG2 Cells

https://doi.org/10.1006/bbrc.2002.6755Get rights and content

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-α), and interleukin-1α (IL-1α) 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-α nor IL-1α 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.

References (40)

Cited by (49)

  • The apoM-S1P axis in hepatic diseases

    2020, Clinica Chimica Acta
    Citation Excerpt :

    Genetically, human APOM is situated on chromosome 6p21.3 in the major histocompatibility complex III, near regions rich in innate immunity and inflammation-related genes. Studies have verified that APOM can be regulated by several inflammatory factors, including platelet-activating factor, lipopolysaccharide and other factors [7–12]. S1P is verified only in apoM-containing HDL, and plasma levels of S1P in apoM-knockout mice are reduced by 46%, whereas they are increased in apoM transgenic mice compared to WT mice [13,14], indicating the important role of apoM in maintaining and regulating S1P levels.

  • Apolipoprotein M

    2015, Clinica Chimica Acta
    Citation Excerpt :

    Specific stimuli, such as zymosan, turpentine and LPS, as well as TNF-α and IL-1, but not IL-6 correlated inversely with apoM transcription levels, the effects of which were mediated by cytokines. However, in another study, IL-1 and TNF-α did not influence apoM levels [69]. The underlying reasons for this discrepancy warrant further investigation.

  • Urinary apolipoprotein M could be used as a biomarker of acute renal injury: An ischemia-reperfusion injury model of kidney in rat

    2013, Transplantation Proceedings
    Citation Excerpt :

    It has recently been found in human colorectal tissues including cancers, cancer-adjacent normal tissues, polyps, and normal mucosa as well as in inflammatory mucosa.11 Several cytokines, including platelet activating factor (PAF), transforming growth factor-beta (TGF-β), epidermal growth factor (EGF), hepatocyte growth factor (HGE), and leptin, are known to regulate hepatic apoM expression in vivo and/or in vitro.12–16 Our previous study demonstrated hepatic apoM expression to be significantly influenced by hepatic IRI, suggesting that apoM has certain characteristics of an acute-phase reactive protein.

View all citing articles on Scopus
1

To whom correspondence and reprint requests should be addressed. Fax: +46 –46 130064. E-mail: [email protected].

View full text