INTERLEUKIN-6 ACTIVATES HEAT-SHOCK PROTEIN 90-BETA GENE-EXPRESSION

The levels of the cytokine interleukin-6 (IL-6) and the heat-shock pro tein hsp90 have both been reported to be elevated in patients with act ive systemic lupus erythematosus (SLE). We show that hsp90 protein acc umulates to increased levels in both HuH7 hepatoma cells and periphera l blood mononuclear cells (PBMCs) treated with IL-6. In PBMCs this eff ect occurs without induction of the other hsps, paralleling the specif ic elevation of hsp90 in SLE. IL-6 is able to activate the hsp90 gene promoter directly; this activation can also be achieved by overexpress ing either of the transcription factors NF-IL-6 or NF-IL-6 beta whose synthesis is induced by IL-6 treatment. Hence the induction of hsp90 p rotein accumulation by IL-6 is likely to be dependent on the enhanced activity of the hsp90 beta gene promoter produced by increased levels of NF-IL-6 and/or NF-IL-6 beta. These effects are discussed in terms o f the role of hsp90 in the normal immune system and the mechanism of i ts activation in patients with SLE.