Regulation of monocyte/macrophage C2 production and HLA-DR expression by IL-4 (BSF-1) and IFN-gamma.
IL-4 was originally described on the basis of its ability to co-stimulate the proliferation of resting B cells treated with anti-IgM. Recently, this cytokine has been shown to have other effects on mast cells, T cells, B cells, and macrophages. We studied the ability of IL-4 to regulate the production of C2 by human monocytes and monocytic cell lines and compared this with stimulation of HLA-DR expression, another recently described activity of IL-4. Responses to IL-4 were compared to IFN-gamma, a cytokine with both activities. IL-4 up-regulated C2 production by human monocytes and this effect was not inhibited by neutralizing anti-IFN-gamma antibody. IL-4 also stimulated C2 production by HL-60 cells that had been pre-treated with vitamin D3 to induce monocytic differentiation. IL-4 did not stimulate C2 production by U937 cells. IFN-gamma, in contrast to IL-4, stimulates C2 production by all three cell types. Although IL-4 increased C2 production by HL-60 cells we could not detect C2 mRNA by Northern blotting. However, co-stimulation of these cells with IL-4 and low concentrations of IFN-gamma resulted in an additive effect on C2 production and a greater increase in C2 mRNA than was seen with IFN-gamma alone. As reported by others, IL-4-stimulated HLA-DR expression by monocytes. In contrast to our findings regarding C2 production, stimulation of HLA-DR expression was inhibited by neutralizing anti-IFN-gamma mAb and IL-4 did not stimulate HLA-DR expression by U937 or HL-60 cells. IFN-gamma stimulated HLA-DR expression by all three cell types. These results identify IL-4 as an additional cytokine able to directly stimulate C2 production by human monocytes and by a monocytic cell line whereas IL-4 stimulation of HLA-DR expression by monocytes appears to be IFN-gamma dependent.
Littman
B H
BH
Rheumatology Section, McGuire V.A. Medical Center, Richmond, VA 23249.
Dastvan
F F
FF
Carlson
P L
PL
Sanders
K M
KM
D000906:Antibodies / Q000502:physiology; D015152:Blotting, Northern; D002460:Cell Line; D003175:Complement C2 / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000302:isolation & purification; D011994:Recombinant Proteins
D000906:Antibodies; D003175:Complement C2; D006684:HLA-DR Antigens; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma