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Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells
W H Ettinger1, V K Varma, M Sorci-Thomas
1Department of Internal Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.
Arteriosclerosis and Thrombosis : a Journal of Vascular Biology
|January 1, 1994
Summary
Cytokines, key inflammation mediators, lower cholesterol by reducing liver apolipoprotein synthesis and secretion. This study shows how inflammatory cytokines impact cholesterol metabolism and apolipoprotein levels.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Cytokines are crucial mediators of inflammation.
- Inflammation is associated with decreased plasma cholesterol levels (acquired hypocholesterolemia).
- A potential mechanism involves reduced hepatic synthesis and secretion of apolipoproteins.
Purpose of the Study:
- To investigate the effect of specific cytokines on apolipoprotein synthesis and secretion in liver cells.
- To determine if cytokines influence apolipoprotein mRNA levels.
- To explore the impact on cholesterol and triglyceride metabolism.
Main Methods:
- Incubation of Hep G2 cells with tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6.
- Measurement of apolipoprotein A-I, apolipoprotein B, and lecithin:cholesterol acyltransferase (LCAT) activity in the cell medium.
- Analysis of cellular apolipoprotein A-I and apolipoprotein B mRNA concentrations.
- Assessment of sterol synthesis and secretion rates using [14C]acetate incorporation.
Main Results:
- Cytokines caused a dose-related decrease in apolipoprotein A-I, apolipoprotein B, and LCAT activity in the medium.
- Cellular apolipoprotein A-I mRNA decreased, but apolipoprotein B mRNA levels were unaffected.
- Triglyceride and cholesterol concentrations were reduced in the medium.
- Interleukin-6 increased sterol synthesis but decreased sterol secretion.
Conclusions:
- These cytokines can reduce the hepatic synthesis and/or secretion of apolipoproteins.
- This cytokine-induced reduction in apolipoproteins may contribute to acquired hypocholesterolemia during inflammation.
- The findings provide insight into the molecular mechanisms linking inflammation and altered lipid metabolism.