Effects of interferon-gamma and tumor necrosis factor-alpha on the expression of an Ia antigen on a murine macrophage cell line.
Cultures of the murine myelomonocytic cell line, WEHI-3, can be induced to express the Class II MHC antigen, I-A, by incubation with rMuIFN-gamma and/or rHuTNF-alpha. A 24-hr incubation with the combination of rMuIFN-gamma (5.6 ng/ml) and rHuTNF-alpha (13 ng/ml) induced the highest level of expression in the cell population (more than 90%), followed by rMuIFN-gamma (75%) and rHuTNF-alpha (33%). Comparison of the level of mRNA for the heavy chain subunit of the I-A molecule, A alpha, indicates that the combination is 10 and 40 times as stimulatory as rMuIFN-gamma and rHuTNF-alpha alone, respectively. Each cytokine treatment induced a time-dependent increase in the level of A alpha mRNA over the 72 hr of incubation examined, although the combination continued to elevate the level of A alpha mRNA above that induced by either cytokine alone. The findings reported here demonstrate that the monokine rHuTNF-alpha can induce I-A antigen expression and A alpha mRNA. Furthermore, stimulation by the combination of rHuTNF-alpha and rMuIFN-gamma is more than additive, relative to the effects of each cytokine as individual agents.
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma