Heat shock protein 90, a potential biomarker for type I diabetes, is secreted by human pancreatic beta cells in response to cytokine stress (BA7P.161)

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Abstract Heat shock protein 90 (HSP90) is a molecular chaperone that regulates diverse cellular processes by facilitating the activities of a wide variety of protein clients. Recent collaborative studies from our lab have shown that serum HSP90 levels are elevated in newly diagnosed type I diabetic patients, thus distinguishing HSP90 as a potential biomarker for this autoimmune disease. The clinical onset of type 1 diabetes (T1D) is known to be associated with insulitis, the infiltration of inflammatory cells into the pancreatic islets. Therefore, to test the hypothesis that inflammatory stress results in HSP90 release from pancreatic islets, we treated primary human cadaveric islets from non-diabetic donors with a cocktail of inflammatory cytokines IFN-γ, TNF-α, and IL-1β and found that increased levels of HSP90 are secreted by cytokine-treated islets. Flow cytometry of dispersed pancreatic islets suggests beta cells may be responsible for the release of this chaperone in response to cytokine treatment. Further studies with cytokine-treated human beta cell lines βLOX5 and 1.1B4 support this finding. In contrast, beta cell lines do not secrete HSP90 upon treatment with thapsigargin, suggesting HSP90 is not released in response to beta cell endoplasmic reticulum stress, which is also known to precede the onset on T1D. Studies are underway to determine the exact mechanism by which HSP90 is released in response to cytokine stress as well as to elucidate the role of HSP90 in T1D etiology.