IL-4 SECRETION AND HISTAMINE-RELEASE BY HUMAN BASOPHILS ARE DIFFERENTIALLY REGULATED BY PROTEIN-KINASE-C ACTIVATION

The role of protein kinase C (PRC) activation was investigated in the secretion of interleukin-4 (IL-4) protein by human basophils, Phorbol myristate acetate (PMA) induced little to no detectable IL-4 protein i n culture supernatants, despite being a potent secretagogue of histami ne release by basophils, In fact, the secretion of IL-4 by basophils s timulated with ionomycin along was down-regulated (30-70%) with the si multaneous addition of PMA. In peripheral blood lymphocytes (PBL), how ever, the combination of ionomycin and PMA were highly synergistic, re sulting in maximum. IL-4 release but at a slower rate, PKC inhibitors reversed these effects on IL-l secretion. In sharp contrast to its inh ibitory effect on IL-4 protein secretion, PMA did not block the accumu lation of IL-4 mRNA in basophils activated by ionomycin. These data su ggest that there are marked differences in the regulatory processes fo r IL-4 transcription, translation, or secretion between basophils and lymphocytes.