Studies on the immunosuppressive properties of 7,25 dihydroxycholesterol--II. Effects on early steps of T-cell activation.
The effects of an oxysterol, 7,25-dihydroxycholesterol (7,25-OHC), cyclosporin A (CsA) and dexamethasone (Dex) on the blastogenic response of murine lymphocytes to various stimuli were investigated. 7,25-OHC markedly depressed the response to Con A, anti-T3 monoclonal antibodies and to the combination phorbol myristate acetate (PMA) + IL-2 and PMA + ionomycin. Dexamethasone was also active within the same range of concentrations. However, it did not inhibit the stimulation induced by PMA + ionomycin. On the other hand, Cs A failed to depress the lymphocyte response to IL-2 + PMA. Therefore, the mechanisms of action involved in the blockage of lymphocyte activation are different for these three compounds. Moreover, we noted that 7,25-OHC was less active upon purified T-cells. Taken together, these results suggest that 7,25-OHC may act at the level of signal transduction across the membrane.
Moog
C
C
Laboratoire de Chimie Organique des Substances Naturelles, UA 31, CNRS, Strasbourg, France.
Luu
B
B
Altmeyer
A
A
Bischoff
P
P
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology
D003524:Cyclosporins; D006888:Hydroxycholesterols; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; C057657:7,25-dihydroxycholesterol; D003208:Concanavalin A; D015759:Ionomycin; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate