Azodicarbonamide as a new T cell immunosuppressant: synergy with cyclosporin A.
We recently demonstrated that azodicarbonamide is an immunosuppressive compound that inhibits calcium mobilization in T lymphocytes. In this study, we show that azodicarbonamide prevents the progression of human CD4+ T lymphocytes into the G1 phase of the cell cycle, inhibits their blastogenesis, down-regulates their membrane expression of CD25 and CD69, and decreases their transcription of cytokine genes. Addition of the calcium ionophore A23187 completely restores T cell proliferation in the presence of azodicarbonamide. Furthermore, azodicarbonamide synergizes with cyclosporin A to inhibit CD4+ T cell proliferation. In conclusion, the immunosuppressive action of azodicarbonamide is mainly related to its effect on the calcium mobilization machinery and is synergistic with that of calcineurin inhibitors.
Tassignon
J
J
CYPRO S.A., 40 avenue J. Wybran, Brussels, B-1070, Belgium.
Vandevelde
M
M
Goldman
M
M
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D001391:Azo Compounds / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007476:Ionophores / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001391:Azo Compounds; D000001:Calcimycin; D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007476:Ionophores; D037181:Lectins, C-Type; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; D000099192:CD69 Antigens; C004525:azodicarbonamide