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The Journal of Immunology, Vol 145, Issue 1 161-166, Copyright © 1990 by American Association of Immunologists
ARTICLES |
JA Elias and V Lentz
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104.
We characterized the effects of rIL-1 and rTNF on human lung fibroblast IL-6 production. rIL-1 was a potent stimulator, rTNF only marginally stimulated, and rIL-1 and rTNF in combination synergistically stimulated IL-6 protein production. These changes were associated with proportionate alterations in IL-6 mRNA accumulation. Nuclear run-on analysis demonstrated that the effects of rIL-1 and rTNF individually were associated with increased IL-6 gene transcription. In contrast, alterations in gene transcription could not fully explain the synergistic effects of rIL-1 and rTNF in combination. However, IL-6 mRNA was significantly more stable in cells stimulated with rIL-1 plus rTNF than in cells stimulated with rIL-1 alone. Thus the synergistic effects of rIL-1 and rTNF in combination were mediated, at least partially, by an alteration in the stability of IL-6 mRNA. Alterations in mRNA stability may be an important mechanism of cytokine-cytokine synergy.
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