Synergism between AS101 and PMA in lymphokine production

B. Sredni, Y. Kalechman, F. Shalit, M. Albeck

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

AS101 [ammonium trichloro (dioxyethylene-o-o') tellurate] has been reported to stimulate normal mouse and human lymphoid cells to proliferate and to produce lymphokines such as interleukin-2 (IL-2) and colony-stimulating factor (CSF), regulators of lymphopoiesis and myelopoiesis. In this study, we demonstrate that the IL-2 secretion and cell proliferation of both human and mouse lymphocytes, and the production of CSF by mouse spleen cells, was significantly enhanced by the synergistic effect of AS101 and phorbol myristate acetate (PMA). AS101-induced activation was found to be very sensitive to inhibition by EGTA, the Ca2+- channel blocker, nifedipine, and cyclosporin A (CsA), an agent which selectively suppresses Ca2+-activated steps in this process. Our results suggest that AS101 may efficiently trigger the Ca2+ signal required to initiate lymphocyte activation, but that the enhancement observed when cells are stimulated with both AS101 and PMA may be due to the generation of a second signal, probably the activation of protein kinase C (PKC). A more thorough understanding of the mechanism of action of the immunomodulator AS101, presently under clinical trials on cancer and AIDS patients, is highly relevant to the assessment of its optimal application.

Original languageEnglish
Pages (from-to)110-116
Number of pages7
JournalImmunology
Volume69
Issue number1
StatePublished - Jan 1990

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