Activation of T-cells by bryostatins: induction of the IL-2 receptor gene transcription and down-modulation of surface receptors
| Autor: | William H. Adler, W. Stratford May, Allan D. Hess, Ahmed H. Esa, William O. Boto |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Bryostatin 1
CD3 Complex T-Lymphocytes Immunology Receptors Antigen T-Cell Down-Regulation Gene Expression Antineoplastic Agents Biology Lymphocyte Activation chemistry.chemical_compound Lactones Cell surface receptor Gene expression medicine Staurosporine Humans Northern blot Bryostatin Receptor Protein kinase C Protein Kinase C Pharmacology Receptors Interleukin-2 Bryostatins Molecular biology Stimulation Chemical chemistry Antigens Surface CD4 Antigens Tetradecanoylphorbol Acetate Macrolides medicine.drug |
| Zdroj: | International journal of immunopharmacology. 12(5) |
| ISSN: | 0192-0561 |
| Popis: | Bryostatins are macrocyclic lactones isolated from the marine bryozoan Bugula neritina . They are currently evaluated for putative antineoplastic activity. Bryostatins bind and activate protein kinase C (PK-C), the cellular receptor for the phorbol esters, and elicit PK-C-dependent cellular functions. Such functions include the expression of the interleukin-2 receptor (IL-2R). Northern blot hybridization with a human IL-2R and an IL-2 cDNA showed that bryostatin 1 (bryo 1), like the phorbol ester, PMA, activates the IL-2R gene. Activation with bryo 1 or PMA in the presence of a calcium ionophore, A23187, increased IL-2 message. These findings indicate that calcium mobilization is necessary for bryo 1 or PMA induced IL-2 gene expression. Unlike PMA, bryo 1 did not cause a vigorous proliferative response of T-lymphocytes unless A23187 was added to the cultures. A bryostatin congener, bryo 13, was inactive in the above assays. Short-term treatment of T-cells with bryo 1 and PMA resulted in an equivalent down-regulation of surface CD3 and CD4 receptors withour affecting the CD8 receptor. Bryo 1 or PMA mediated expression of surface IL-2R and T-cell proliferation induced by bryo 1 or PMA were sensitive to inhibition by the PK-C antagonists staurosporine (Sts) and H-7. In contrast, CD4 and CD3 down regulation were resistant to H-7, but could be blocked by Sts, although the Sts concentration required to block bryo 1 or PMA-induced down-modulation was 2.5-fold higher than required to inhibit IL-2R expression and T-cell proliferation. These results indicate that bryostatins activate T-cells through PK-C. |
| Databáze: | OpenAIRE |
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