IL-4 secretion and histamine release by human basophils are differentially regulated by protein kinase C activation.
The role of protein kinase C (PKC) 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 in culture supernatants, despite being a potent secretagogue of histamine release by basophils. In fact, the secretion of IL-4 by basophils stimulated with ionomycin alone was down-regulated (30-70%) with the simultaneous addition of PMA. In peripheral blood lymphocytes (PBL), however, the combination of ionomycin and PMA were highly synergistic, resulting in maximum IL-4 release but at a slower rate. PKC inhibitors reversed these effects on IL-4 secretion. In sharp contrast to its inhibitory effect on IL-4 protein secretion, PMA did not block the accumulation of IL-4 mRNA in basophils activated by ionomycin. These data suggest that there are marked differences in the regulatory processes for IL-4 transcription, translation, or secretion between basophils and lymphocytes.
Schroeder
J T
JT
The Johns Hopkins University School of Medicine, Division of Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA. schray@welchlink.welch.jhu.edu
Howard
B P
BP
Jenkens
M K
MK
Kagey-Sobotka
A
A
Lichtenstein
L M
LM
MacGlashan
D W
DW
D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism* / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007476:Ionophores; D015847:Interleukin-4; D015759:Ionomycin; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium