Interferon-gamma Inhibits Macrophage Apolipoprotein E Production by Posttranslational Mechanisms

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1993 May 1

PMID 8486772

Citations 25

Authors

K Brand

N Mackman

L K Curtiss

Affiliations

Soon will be listed here.

Abstract

Macrophage-derived apolipoprotein (apo) E and multimers of a synthetic apo E-peptide display monokine-like functions by inhibiting mitogen- or antigen-driven lymphocyte proliferation. This study demonstrated how the target lymphocyte itself can modulate macrophage apo E production. The lymphokine interferon-gamma (IFN) dramatically inhibited the accumulation of apo E in the supernatant of human monocytic THP-1 cells when present during phorbol myristate acetate-induced differentiation. A similar effect was observed when IFN was added to differentiated THP-1 cells. Treatment with IFN did not change the steady-state levels of apo E mRNA. Furthermore, in the presence of IFN no increased degradation or increased uptake of extracellular apo E was detected. Pulse-chase experiments indicated that IFN reduced the accumulation of extracellular apo E and increased the degradation of intracellular apo E. The inhibitory effect of IFN on apo E production also was observed in human monocyte-derived macrophages. Thus, our data demonstrated that IFN inhibited macrophage apo E production by posttranslational mechanisms. This represents a previously uncharacterized immunoregulatory interaction and lends further support to a relationship between lipid metabolism and the immune system.

Citing Articles

ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia-driven hematopoiesis & inflammation via extracellular vesicles.

Phu T, Ng M, Vu N, Gao A, Raffai R J Extracell Vesicles. 2023; 12(8):e12345.

PMID: 37593979 PMC: 10436255. DOI: 10.1002/jev2.12345.

Blood and brain transcriptome analysis reveals APOE genotype-mediated and immune-related pathways involved in Alzheimer disease.

Panitch R, Hu J, Xia W, Bennett D, Stein T, Farrer L Alzheimers Res Ther. 2022; 14(1):30.

PMID: 35139885 PMC: 8830081. DOI: 10.1186/s13195-022-00975-z.

Interactions of SARS-CoV-2 with the Blood-Brain Barrier.

Erickson M, Rhea E, Knopp R, Banks W Int J Mol Sci. 2021; 22(5).

PMID: 33800954 PMC: 7961671. DOI: 10.3390/ijms22052681.

Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation.

Lanfranco M, Sepulveda J, Kopetsky G, Rebeck G Glia. 2021; 69(6):1478-1493.

PMID: 33556209 PMC: 8717762. DOI: 10.1002/glia.23974.

Comparative Proteomic Analysis of Serum from Pigs Experimentally Infected with , and .

Gondek M, Herosimczyk A, Knysz P, Ozgo M, Lepczynski A, Szkucik K Pathogens. 2020; 9(1).

PMID: 31940868 PMC: 7168678. DOI: 10.3390/pathogens9010055.

References

Brand K, FOWLER B, Edgington T, Mackman N . Tissue factor mRNA in THP-1 monocytic cells is regulated at both transcriptional and posttranscriptional levels in response to lipopolysaccharide. Mol Cell Biol. 1991; 11(9):4732-8. PMC: 361371. DOI: 10.1128/mcb.11.9.4732-4738.1991. View

Sechler J, Malech H, White C, Gallin J . Recombinant human interferon-gamma reconstitutes defective phagocyte function in patients with chronic granulomatous disease of childhood. Proc Natl Acad Sci U S A. 1988; 85(13):4874-8. PMC: 280539. DOI: 10.1073/pnas.85.13.4874. View

Auwerx J, Deeb S, Brunzell J, Peng R, Chait A . Transcriptional activation of the lipoprotein lipase and apolipoprotein E genes accompanies differentiation in some human macrophage-like cell lines. Biochemistry. 1988; 27(8):2651-5. DOI: 10.1021/bi00408a003. View

Takagi Y, DYER C, Curtiss L . Platelet-enhanced apolipoprotein E production by human macrophages: a possible role in atherosclerosis. J Lipid Res. 1988; 29(7):859-67. View

Faltynek C, FINCH L, Miller P, Overton W . Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines. J Immunol. 1989; 142(2):500-8. View

Heidenreich S, Gong J, Schmidt A, Nain M, Gemsa D . Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. J Immunol. 1989; 143(4):1198-205. View

Hansson G, Holm J, Jonasson L . Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol. 1989; 135(1):169-75. PMC: 1880219. View

Mazzone T, Basheeruddin K, Poulos C . Regulation of macrophage apolipoprotein E gene expression by cholesterol. J Lipid Res. 1989; 30(7):1055-64. View

Menju M, Tajima S, Yamamoto A . Expression of the apolipoprotein E gene in a human macrophage-like cell line, THP-1. J Biochem. 1989; 106(3):505-10. DOI: 10.1093/oxfordjournals.jbchem.a122882. View

10.

Young H, Hardy K . Interferon-gamma: producer cells, activation stimuli, and molecular genetic regulation. Pharmacol Ther. 1990; 45(1):137-51. DOI: 10.1016/0163-7258(90)90012-q. View

11.

Virca G, Northemann W, Shiels B, Widera G, Broome S . Simplified northern blot hybridization using 5% sodium dodecyl sulfate. Biotechniques. 1990; 8(4):370-1. View

12.

Sparks J, Sparks C . Insulin modulation of hepatic synthesis and secretion of apolipoprotein B by rat hepatocytes. J Biol Chem. 1990; 265(15):8854-62. View

13.

Rothman J, Raymond C, Gilbert T, OHara P, Stevens T . A putative GTP binding protein homologous to interferon-inducible Mx proteins performs an essential function in yeast protein sorting. Cell. 1990; 61(6):1063-74. DOI: 10.1016/0092-8674(90)90070-u. View

14.

Jonasson L, Hansson G, Bondjers G, Noe L, Etienne J . Interferon-gamma inhibits lipoprotein lipase in human monocyte-derived macrophages. Biochim Biophys Acta. 1990; 1053(1):43-8. DOI: 10.1016/0167-4889(90)90024-8. View

15.

Sato R, Imanaka T, Takatsuki A, Takano T . Degradation of newly synthesized apolipoprotein B-100 in a pre-Golgi compartment. J Biol Chem. 1990; 265(20):11880-4. View

16.

ARAI K, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T . Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990; 59:783-836. DOI: 10.1146/annurev.bi.59.070190.004031. View

17.

Lewis D, Wilson C . Gamma-interferon: an immunoregulatory lymphokine with immunotherapeutic potential. Pediatr Infect Dis J. 1990; 9(9):642-51. View

18.

Matsumoto A, Naito M, Itakura H, Ikemoto S, Asaoka H, Hayakawa I . Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions. Proc Natl Acad Sci U S A. 1990; 87(23):9133-7. PMC: 55118. DOI: 10.1073/pnas.87.23.9133. View

19.

Terkeltaub R, DYER C, Martin J, Curtiss L . Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to stimulate neutrophils. Characterization of intraarticular apo E and demonstration of apo E binding to urate crystals in vivo. J Clin Invest. 1991; 87(1):20-6. PMC: 294981. DOI: 10.1172/JCI114971. View

20.

Watanabe Y, Jacob C . Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. J Immunol. 1991; 146(3):899-905. View