Transforming growth factor-beta regulation of IL-6 production by unstimulated and IL-1-stimulated human fibroblasts.
We characterized the ability of transforming growth factor-beta 1 (TGF-beta 1) and transforming growth factor-beta 2 (TGF-beta 2) to regulate IL-6 production by unstimulated and rIL-1-stimulated lung fibroblasts. rTGF-beta 1-, purified TGF-beta 1-, and purified TGF-beta 2-stimulated fibroblasts produced IL-6 bioactivity as assessed with the B9 hybridoma proliferation assay. These TGF-beta moieties also bidirectionally regulated the IL-6 production of rIL-1-stimulated fibroblasts. The addition of TGF-beta to cultures in which fibroblasts were vigorously stimulated with rIL-1 resulted in an inhibition of fibroblast IL-6 production and mRNA accumulation. In contrast, the addition of TGF-beta to cultures in which fibroblasts were incubated with suboptimal concentrations of rIL-1 resulted in a synergistic increase in IL-6 production and mRNA accumulation [corrected]. Nuclear run-on analysis demonstrated that IL-6 gene [corrected] transcription was synergistically augmented when rTGF-beta 1 was combined with suboptimal concentrations of rIL-1. These studies demonstrate that TGF-beta stimulates fibroblast IL-6 production. They also show that TGF-beta can augment or inhibit the IL-6 production of IL-1-stimulated fibroblasts. Lastly, [corrected] they demonstrate that the stimulatory effects of TGF-beta are, at least partially, mediated by alterations in IL-6 gene transcription. TGF-beta may be an important regulator of IL-6 production. stimulated fibroblasts. Last, they demonstrate that the stimulatory effects of TGF-beta are, at least partially, mediated by alterations in IL-6 gene transcription. TGF-beta may be an important regulator of IL-6 production.
Elias
J A
JA
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
Lentz
V
V
Cummings
P J
PJ
D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta