| Heat shock protein 90 inhibition in autoimmunity to type VII collagen: evidence that non-malignant plasma cells are not therapeutic targets. | |
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MedLine Citation:
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PMID: 21490339 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Blocking heat shock protein 90 (Hsp90) induces death of malignant plasma cells by activation of the unfolded protein response (UPR), a signaling pathway activated by accumulation of misfolded proteins within the endoplasmatic reticulum. We hypothesized that non-transformed plasma cells are also hypersensitive to Hsp90 inhibition owing to their high amount of protein biosynthesis. To study this, two different Hsp90 inhibitors, the geldanamycin derivative 17-DMAG or the nontoxic peptide derivative TCBL-145, were applied to mice with experimental epidermolysis bullosa acquisita, an autoimmune bullous disease characterized by autoantibodies against type VII collagen of the dermal-epidermal junction. Both inhibitors ameliorated clinical disease of type VII collagen-immunized mice, suppressed autoantibody production, and reduced dermal neutrophilic infiltrate. Interestingly, total plasma cells numbers, type VII collagen-specific plasma cells and germinal center B cells were unaffected by anti-Hsp90 treatment in vivo. However, T cell proliferation was potently inhibited, as evidenced by reduced response of isolated lymph node cells from immunized mice to in vitro re-stimulation with anti-CD3/CD28 antibody or autoantigen in presence of Hsp90 inhibitors. Our results suggest that Hsp90 blockade has no impact on normal or autoreactive plasma cells in vivo and indentify T cells as targets of anti-Hsp90 treatment in autoimmunity to type VII collagen. |
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Authors:
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Michael Kasperkiewicz; Ralf Müller; Rudolf Manz; Moritz Magens; Christoph M Hammers; Csaba Somlai; Jürgen Westermann; Enno Schmidt; Detlef Zillikens; Ralf J Ludwig; Antal Orosz |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-13 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Dermatology, University of Luebeck, Luebeck, Germany; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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