Linked Life Data

21490339

Source:http://linkedlifedata.com/resource/pubmed/id/21490339

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2011-6-10
pubmed:abstractText
Blocking heat-shock protein 90 (Hsp90) induces death of malignant plasma cells by activation of the unfolded protein response, a signaling pathway activated by accumulation of misfolded proteins within the endoplasmic reticulum. We hypothesized that nontransformed plasma cells are also hypersensitive to Hsp90 inhibition because of their high amount of protein biosynthesis. To investigate this hypothesis, 2 different Hsp90 inhibitors, the geldanamycin derivative 17-DMAG and 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 auto-antibody production, and reduced dermal neutrophilic infiltrate. Interestingly, total plasma cell 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 the reduced response of isolated lymph node cells from immunized mice to in vitro restimulation with anti-CD3/CD28 antibody or autoantigen in the 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6135-42
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Heat-shock protein 90 inhibition in autoimmunity to type VII collagen: evidence that nonmalignant plasma cells are not therapeutic targets.
pubmed:affiliation
Department of Dermatology, University of Lübeck, Lübeck, Germany. Michael.Kasperkiewicz@uk-sh.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't