Effects of platelet-activating factor, tumor necrosis factor, and interleukin-1alpha on the expression of apolipoprotein M in HepG2 cells.

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

Apolipoproteins B : metabolism

Apolipoproteins B : genetics

Apolipoproteins : metabolism

Apolipoproteins : genetics

Apolipoprotein A-I : metabolism

Apolipoprotein A-I : genetics

Interleukin-1 : pharmacology

Leucine : analogs & derivatives

Leucine : pharmacology

Liver Neoplasms : drug therapy

Tumor Necrosis Factor : pharmacology

Cultured

Tumor Cells

Non-U.S. Gov't

Support

Messenger : metabolism

RNA

Platelet Activating Factor : pharmacology

Liver Neoplasms : metabolism

Platelet Activating Factor : antagonists & inhibitors

Apolipoproteins E : genetics

Apolipoproteins E : metabolism

Dose-Response Relationship

Drug

Gene Expression : drug effects

Hepatoblastoma : drug therapy

Hepatoblastoma : metabolism

Human

Imidazoles : pharmacology

Publikations- och innehållstyp

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