title: Heat shock protein 90: a pathophysiological factor and novel treatment target in autoimmune bullous skin diseases.
abstract: The chaperone heat shock protein 90 (Hsp90), a cell stress-inducible molecule that regulates activity of many client proteins responsible for cellular growth, differentiation and apoptosis, has been proposed as an important therapeutic target in patients with malignancies. More recently, its active participation in (auto)immune processes has been recognized as evidenced by amelioration of inflammatory disease pathways through pharmacological inhibition of Hsp90 in rodent models of autoimmune encephalomyelitis, rheumatoid arthritis and systemic lupus erythematosus. Based on own current research results, this viewpoint essay provides important insights that Hsp90 is also involved as a notable pathophysiological factor in autoimmune blistering dermatoses including epidermolysis bullosa acquisita, bullous pemphigoid and possibly dermatitis herpetiformis. The observed in vitro, ex vivo and in vivo efficacy of anti-Hsp90 treatment in experimental models of autoimmune bullous diseases and its underlying multimodal anti-inflammatory mechanisms of interference with key contributors to autoimmune-mediated blister formation supports the introduction of selective non-toxic Hsp90 inhibitors into the clinical setting for the treatment of patients with these disorders.
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tukaj
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kasperkiewicz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000503:physiopathology; D016227:Benzoquinones / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D003874:Dermatitis Herpetiformis / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016107:Epidermolysis Bullosa Acquisita / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D058990:Molecular Targeted Therapy; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D010391:Pemphigoid, Bullous / Q000188:drug therapy / Q000276:immunology; D016897:Respiratory Burst / Q000187:drug effects; D012872:Skin Diseases, Vesiculobullous / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D016227:Benzoquinones; D016207:Cytokines; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009842:Oligopeptides; C000607511:TCBL-145 peptide; C448659:17-(dimethylaminoethylamino)-17-demethoxygeldanamycin
keywords: autoimmunity; bullous disease; heat shock protein 90; inflammation