The weak immunosuppressant cyclosporine D as well as the immunologically inactive cyclosporine H are potent inhibitors in vivo of phorbol ester TPA-induced biological effects in mouse skin and of Ca2+/calmodulin dependent EF-2 phosphorylation in vitro.
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| Abstract |
Various biological effects induced by the tumor promoting phorbol ester TPA in mouse skin are comparably suppressed by the immunologically inactive cyclosporine H (CsH) and by the strongly immunosuppressive cyclosporine A (CsA). These effects inhibited include the development of edema, stimulation of alkaline phosphatase activity, DNA and protein synthesis, as well as tumor promotion. Furthermore, CsH, like CsA, inhibits the Ca2+/calmodulin-dependent phosphorylation of the elongation factor 2 (EF-2) in vitro and the TPA-induced increases in the amount of EF-2 in vivo. Similar observations were made using the weak immunosuppressant CsD. We conclude from these results that the ability of cyclosporines to act as immunosuppressants and their ability to inhibit TPA-effects are based on two different mechanisms of action. Inhibition of TPA-effects may involve suppression of calmodulin-dependent processes, such as augmentation and phosphorylation of EF-2.
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| Authors | M Gschwendt, W Kittstein, F Marks |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 150 Issue 2 Pg. 545-51 (Jan 29 1988) ISSN: 0006-291X [Print] United States |
| PMID | 3342035 (Publication Type: Comparative Study, Journal Article) |
| Chemical References |
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