Inhibitory effects of N-acetylcysteine on scavenger receptor class A expression in human macrophages.

• OBJECTIVE: The formation of foam cells from monocyte-derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N-acetylcysteine on the expression of the class A scavenger receptor (SR-A) types I and II in human macrophages. DESIGN: Monocytes and macrophages from healthy blood donors and plaque-derived macrophages from patients undergoing carotid endarterectomy were used for experiments. SR-A mRNA was analysed with quantitative and semiquantitative reverse transcription-polymerase chain reaction, and ligand binding and uptake were assessed with 125I-labelled acetylated low-density lipoprotein (LDL). RESULTS: Incubation of monocytes and monocyte-derived macrophages with N-acetylcysteine decreased both SR-A I and II mRNA expression. N-Acetylcysteine also reduced SR-A mRNA in lesion-derived cells. Binding and uptake of 125I-acetylated LDL was decreased after brief incubation with N-acetylcysteine. After longer periods of incubation with N-acetylcysteine we observed an increased degradation of lipoproteins. CONCLUSIONS: Our results imply that N-acetylcysteine leads to a decrease in SR-A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Acetylcysteine

pharmacology

Cell Adhesion Molecules

metabolism

Cells

Cultured

Centrifugation

Density Gradient

Glutathione

analysis

Humans

Macrophages

metabolism

Promoter Regions

Genetic

Receptors

Immunologic

metabolism

Receptors

Scavenger

Scavenger Receptors

Class A

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