Interleukin 6 activates heat-shock protein 90<i>β</i> gene expression

The levels of the cytokine interleukin-6 (IL-6) and the heat-shock protein hsp90 have both been reported to be elevated in patients with active systemic lupus erythematosus (SLE). We show that hsp90 protein accumulates to increased levels in both HuH7 hepatoma cells and peripheral blood mononuclear cells (PBMCs) treated with IL-6. In PBMCs this effect occurs without induction of the other hsps, paralleling the specific elevation of hsp90 in SLE. IL-6 is able to activate the hsp90 gene promoter directly; this activation can also be achieved by overexpressing either of the transcription factors NF-IL-6 or NF-IL-6β whose synthesis is induced by IL-6 treatment. Hence the induction of hsp90 protein accumulation by IL-6 is likely to be dependent on the enhanced activity of the hsp90β gene promoter produced by increased levels of NF-IL-6 and/or NF-IL-6β. These effects are discussed in terms of the role of hsp90 in the normal immune system and the mechanism of its activation in patients with SLE.