Induction of heat shock protein in monocytic cells by oxidized low density lipoprotein.
The atherosclerotic lesion may be characterized as a chronic inflammatory process, and oxidized LDL is believed to be a key event in the development of atherosclerosis, though the mechanisms by which oxidized LDL exerts its proatherogenic properties are largely unknown. Heat shock proteins (hsp) are a group of proteins with a highly conserved structure and of these, hsp60 has been suggested to play a role in autoimmunity due to T lymphocyte crossreactivity between bacterial and human hsp60. The present study was designed to investigate the effects of oxidized LDL on the expression of hsp60 using the monocytic cell lines U937 and HL60 as models. The expression of hsp60 was determined by using monoclonal antibodies to hsp60 in FACScan, Western blot, and a sandwich ELISA. The results show that hsp60 is induced in both cell types after 2 h exposure to oxidized LDL, with a maximal effect at 20 micrograms/ml for U937 cells and 5 micrograms/ml for HL60 cells. A close to 3-fold increase in the expression of hsp60 was seen after culturing oxidized LDL (20 micrograms/ml) treated U937 cells for a period of 24 h. Interleukin 1-beta had similar effects on hsp60 expression to oxidized LDL. The results indicate that expression of hsp60 by monocytes in the vascular wall may be enhanced by oxidized LDL. It is thus possible that the chronic inflammatory process characterizing atherosclerosis is perpetuated by autoreactive T cells, which recognize hsp60 expressed by monocytes, induced by oxidized LDL.
Frostegård
J
J
Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Kjellman
B
B
Gidlund
M
M
Andersson
B
B
Jindal
S
S
Kiessling
R
R
D001161:Arteriosclerosis / Q000378:metabolism; D001327:Autoimmune Diseases / Q000378:metabolism; D018834:Chaperonin 60 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018834:Chaperonin 60; D007375:Interleukin-1; D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D007371:Interferon-gamma