Aberrant Expression and Secretion of Heat Shock Protein 90 in Patients with Bullous Pemphigoid
Open Access
- 30 July 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (7), e70496
- https://doi.org/10.1371/journal.pone.0070496
Abstract
The cell stress chaperone heat shock protein 90 (Hsp90) has been implicated in inflammatory responses and its inhibition has proven successful in different mouse models of autoimmune diseases, including epidermolysis bullosa acquisita. Here, we investigated expression levels and secretory responses of Hsp90 in patients with bullous pemphigoid (BP), the most common subepidermal autoimmune blistering skin disease. In comparison to healthy controls, the following observations were made: (i) Hsp90 was highly expressed in the skin of BP patients, whereas its serum levels were decreased and inversely associated with IgG autoantibody levels against the NC16A immunodominant region of the BP180 autoantigen, (ii) in contrast, neither aberrant levels of circulating Hsp90 nor any correlation of this protein with serum autoantibodies was found in a control cohort of autoimmune bullous disease patients with pemphigus vulgaris, (iii) Hsp90 was highly expressed in and restrictedly released from peripheral blood mononuclear cells of BP patients, and (iv) Hsp90 was potently induced in and restrictedly secreted from human keratinocyte (HaCaT) cells by BP serum and isolated anti-BP180 NC16A IgG autoantibodies, respectively. Our results reveal an upregulated Hsp90 expression at the site of inflammation and an autoantibody-mediated dysregulation of the intracellular and extracellular distribution of this chaperone in BP patients. These findings suggest that Hsp90 may play a pathophysiological role and represent a novel potential treatment target in BP.This publication has 40 references indexed in Scilit:
- Pemphigoid diseasesThe Lancet, 2013
- A fragment of secreted Hsp90α carries properties that enable it to accelerate effectively both acute and diabetic wound healing in miceJCI Insight, 2011
- Hsp40 proteins modulate humoral and cellular immune response in rheumatoid arthritis patientsCell Stress and Chaperones, 2010
- The regulatory mechanism of Hsp90α secretion and its function in tumor malignancyProceedings of the National Academy of Sciences of the United States of America, 2009
- Significance of heat shock proteins in the skin upon UV exposureFrontiers in Bioscience-Landmark, 2009
- Transforming Growth Factor α (TGFα)-Stimulated Secretion of HSP90α: Using the Receptor LRP-1/CD91 To Promote Human Skin Cell Migration against a TGFβ-Rich Environment during Wound HealingMolecular and Cellular Biology, 2008
- Heat shock proteins 60 and 70 expression of cutaneous lichen planus: comparison with normal skin and psoriasis vulgaris*Journal of Cutaneous Pathology, 2004
- Blockage of HSP 90 modulates Helicobacter pylori-induced IL-8 productions through the inactivation of transcriptional factors of AP-1 and NF-κBBiochemical and Biophysical Research Communications, 2004
- Roles of heat-shock proteins in innate and adaptive immunityNature Reviews Immunology, 2002
- EXPRESSION OF HEAT SHOCK PROTEINS IN HEAVY METAL-PROVOKED INFLAMED HUMAN SKINImmunopharmacology and Immunotoxicology, 2002