The Autoantigenic Proinsulin B-Chain Peptide B11-23 Synergises with the 70 kDa Heat Shock Protein DnaK in Macrophage Stimulation

Autor: Elias Blasius, Elke Gülden, Hubert Kolb, Christiane Habich, Volker Burkart
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Journal of Diabetes Research, Vol 2018 (2018)
Druh dokumentu: article
ISSN: 2314-6745
2314-6753
DOI: 10.1155/2018/4834673
Popis: Background. Heat shock proteins (Hsp) act as intracellular chaperones and in addition are used as adjuvant in vaccines of peptides complexed with recombinant Hsp. By interacting with autologous peptides, Hsp may promote the induction of autoimmune reactivity. Objective. Here, we analysed whether the effect of Hsp on macrophages is modulated by insulin peptides known to interact with Hsp. Results. Combinations of the 70 kDa Hsp DnaK with peptide B11-23 from the core region of the proinsulin B-chain induced the release of the inflammatory mediators interleukin-6, tumor necrosis factor α, and interleukin-1β from cells of human and murine macrophage lines. In parallel, there was high-affinity binding of B11-23 to DnaK. DnaK mixed with peptides from other regions of the insulin molecule did not stimulate cytokine secretion. DnaK alone induced little cytokine production, and peptides alone induced none. Conclusion. The macrophage-stimulating potential of Hsp70 family proteins when combined with the proinsulin B-chain peptide B11-23 may contribute to the immunodominance of this peptide in the development of beta cell-directed autoimmunity in type 1 diabetes.
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