Glatiramer acetate blocks the activation of THP-1 cells by interferon-gamma.
Glatiramer acetate (previously known as copolymer 1) is a synthetic copolymer of four amino acids that has been approved for use in the treatment of multiple sclerosis. It has been shown to suppress myelin antigen specific T cell activation by competing with these antigens at the major histocompatibility complex class II binding site and by inducing antigen specific suppressor T cells. In this study we investigated the effects of glatiramer acetate on the human monocytic cell line, THP-1, activated by lipopolysaccharide and interferon-gamma as a model for macrophages. At non-toxic concentrations of glatiramer acetate there were dose dependent reductions in the percentage of cells expressing human leukocyte DR and DQ antigen as well as in mean fluorescence intensity by flow cytometry. Production of tumor necrosis factor-alpha and the lysosomal cysteine proteinase cathepsin B were markedly inhibited, but production of interleukin-1 increased. These results suggest that glatiramer acetate might alter macrophage effector function and suggest that further studies in human monocytes and macrophages are warranted.
Li
Q
Q
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Milo
R
R
Panitch
H
H
Swoveland
P
P
Bever
C T
CT
D002401:Cathepsin B / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II; D000068717:Glatiramer Acetate; D006683:HLA-DQ Antigens / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects*
D016207:Cytokines; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D010455:Peptides; D011994:Recombinant Proteins; D000068717:Glatiramer Acetate; D007371:Interferon-gamma; D002401:Cathepsin B