IL-1 and tumor necrosis factor-alpha each up-regulate both the expression of IFN-gamma receptors and enhance IFN-gamma-induced HLA-DR expression on human monocytes and a human monocytic cell line (THP-1).
Stimulation of human blood monocytes (adherent mononuclear cells) and the monocytic cell line, THP-1, by IL-1 or TNF-alpha leads to the up-regulation of IFN-gamma receptors. Scatchard analysis using 125I-IFN-gamma revealed a twofold increase in the number of IFN-gamma receptors on THP-1 cells without an alteration in the affinity of the receptor. The potential functional significance of this induction of IFN-gamma receptors on monocytes and THP-1 cells was investigated by examining the effect of IFN-gamma on MHC class II Ag expression by these cells. Both IL-1 and TNF-alpha enhanced the IFN-gamma-induced HLA-DR expression (> twofold) and this effect was inhibited by antibody to IFN-gamma. In the case of human monocytes, IL-1 or TNF-alpha, each by themselves also increased HLA-DR expression, which was also abrogated by antibody to IFN-gamma. The data suggest that the immunopotentiating effects of IL-1 and TNF-alpha are mediated in part by enhancing IFN-gamma receptor expression on monocytes and macrophages. This presumably would increase the capacity of IFN-gamma to activate macrophages, enabling them to express HLA-DR and present Ag more effectively.
Krakauer
T
T
Medical Division, USAMRIID, Fort Detrick, Frederick, MD 21702-5011.
Oppenheim
J J
JJ
D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000096743:Interferon gamma Receptor
D006684:HLA-DR Antigens; D007371:Interferon-gamma; D007375:Interleukin-1; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor