title: Deficient heat shock protein 70 response to stress in leukocytes at onset of type 1 diabetes.
abstract: Type 1 diabetes is caused by the immune-mediated destruction of pancreatic beta cells. Animal models of the disease demonstrate an increased susceptibility of beta cells to immunological attacks due to their defective stress-responsiveness. To investigate the stress-responsiveness in human type 1 diabetes we analyzed the heat-inducibility of the dominant stress protein heat shock protein (Hsp)70 in diabetic patients at different disease stages. At diabetes-manifestation heat-induced Hsp70 levels in peripheral blood mononuclear cells (PBMC) reached only about 25% of the levels expressed by heat-treated PBMC from non-diabetic subjects (p<0.05). Heat-responsiveness improved with disease duration and was re-established at more than eight months after disease-manifestation. Hyperthermia-induced Hsp70 expression was decreased by the T-helper 1-associated cytokine interferon-gamma and increased by the T-helper 2-associated transforming growth factor-beta. We conclude that impaired cellular stress-responsiveness, aggravated by the inflammatory milieu at the onset of type 1 diabetes, contributes to disease manifestation.
authors.affiliation: Institute of Clinical Diabetes Research, German Diabetes Center at the Heinrich-Heine-University, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Burkart
authors.forename: Leif
authors.initials: L
authors.lastname: Germaschewski
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bellmann
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D018840:HSP70 Heat-Shock Proteins