The mechanism of interleukin 4-induced down-regulation of CD38 on human B cells.
Exposure of Farage, a human B-cell line, to interleukin 4 (IL4) reduced the amount of CD38 antigen on the surface of the cells and in cell lysates. No evidence was obtained for accelerated breakdown, shedding, or internalization of CD38 molecules following IL4 treatment, nor the accumulation of CD38 molecules in the cell interior. The inhibition of protein synthesis with cycloheximide (CXM) diminished the down-regulation of CD38 induced by IL4. CXM decreased the expression of CD38 in Farage cells with arrested mitosis, and IL4 failed to further reduce CD38 expression. Staurosporine, an inhibitor of serine/threonine protein kinases, and H7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine), a preferential inhibitor of protein kinase C (PKC), abrogated the effect of IL4 on CD38, while inhibitors of other serine protein kinases W7 (N-(aminohexyl)-5-chloro-1-naphthalenesulfoamide) and H8 (N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide) failed to interfere with the effect of IL4. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, resembled IL4 in decreasing the expression of CD38, and either staurosporine or H7 abolished this effect. Genistein, an inhibitor of tyrosine kinases, increased the expression of CD38, but failed to abrogate the inhibitory effect of IL4 on CD38. It is concluded that serine/threonine protein kinases mediated the IL4-induced down-regulation of the expression of CD38 molecules in B cells.
Shubinsky
G
G
The Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Schlesinger
M
M
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000276:immunology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D011500:Protein Synthesis Inhibitors; D015847:Interleukin-4; D003513:Cycloheximide; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1