Interferon-beta-1b and interferon-gamma have similar inhibitory effects on apolipoprotein-E production in the monocyte/macrophage.
Apolipoprotein-E (Apo-E) is the major lipid carrier in the brain, and is therefore important in the recyding of lipids and cholesterol to regenerating neurons during the remission phase of multiple sclerosis (MS). Interferon (IFN)-gamma has been shown to inhibit Apo-E production by a mainly post-transcriptional method in a macrophage cell line, and reduced Apo-E in cerebrospinal fluid is noted during the remission phase in patients. IFN-beta-1b is a recombinantly produced, anti-inflammatory cytokine, which has been shown to reduce the severity of MS relapses and reduce relapse rate. We have examined the effects of IFN-gamma and IFN-beta-1b on the production of Apo-E mRNA, cellular protein and secreted protein in primary monocytes derived from donor blood. IFN-beta-1b does not relieve the dose-dependent inhibition of Apo-E seen with IFN-gamma at up to 100 U/ml in these cells, and when used alone inhibits Apo-E production in a dose-dependent manner. This inhibition by IFN-beta-1b was seen to be at a transcriptional level, and dose dependent up to 100 U/ml. Apo-E genotype, which has also been linked to failure to recover from MS relapses, did not affect this inhibition. The mode of action of IFN-beta-1b in MS is therefore not thought to be through modification of Apo-E production.
O'Toole
D
D
Department of Biochemistry, Trinity College, University of Dublin, Ireland. dotoole@tcd.ie
Love
W C
WC
D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects; D004347:Drug Interactions; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*
D001057:Apolipoproteins E; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a