RT-PCR study on the effects of minimally modified low-density lipoproteins and probucol treatment on gene expressions of interleukin-1 and platelet-derived growth factor B-chain in human peripheral blood mononuclear cells.
Oxidatively modified low-density lipoprotein has been identified in early atherosclerotic lesions and may play an important role in atherogenesis. Minimally modified low-density lipoprotein (MM-LDL) derived by prolonged storage under sterile conditions results in mild oxidation and is recognised by the LDL receptor rather than the scavenger receptor. Therefore, it may be closer to the real pathophysiological circumstances in the initial state of atherosclerosis. Using a reverse transcription-polymerase chain reaction (RT-PCR) technique, the present study demonstrates that MM-LDL is capable of inducing gene expression of both interleukin-1 alpha (IL-1 alpha) and interleuking-1 beta (IL-1 beta) in human peripheral blood mononuclear cells in a dose-dependent manner. Concomitant treatment of the cells with the anti-oxidant probucol results in an inhibitory effect in steady-state levels of both IL-1 alpha and IL-1 beta mRNA and the effects were also shown in a dose-dependent fashion. We also found an inhibitory effect of MM-LDL on gene expression of platelet-derived growth factor B chain (PDGF-B) mRNA levels by mononuclear cells. Hence MM-LDL is biologically active and may contribute to the early stages of atherogenesis by stimulating the inflammatory cytokine IL-1 and the efficacy of probucol in inhibiting the progression of atherosclerosis may be due, both to its inhibition of IL-1 expression by intimal macrophages, and its prevention of LDL oxidation.
Li
S R
SR
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, Charterhouse Square, London, UK.
Forster
L A
LA
Anggård
E E
EE
Ferns
G A
GA
D000328:Adult; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011341:Probucol / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
D007375:Interleukin-1; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D011341:Probucol