Heat shock proteins in middle ear cholesteatoma.
Heat shock proteins (HSPs), particularly HSP60 and HSP70, may have integral roles in several aspects of the pathogenesis of acquired cholesteatoma. Cholesteatoma is usually associated with an inflammatory reaction occurring in the middle ear cavity, leading to proliferation, differentiation, and programmed cell death of keratinocytes. The presence of HSP60 and HSP70 in cholesteatoma was demonstrated by the immunoblotting assay with specific anti-HSP60 and anti-HSP70 antibodies after protein extraction. The distribution of HSP60 and HSP70 in the cholesteatoma tissues was studied immunohistochemically with paraffin-embedded sections. HSP60 and HSP70 appeared to be localized in the cytoplasm of keratinocytes in all layers of the epithelium of cholesteatoma. Moreover, HSP70 was found in the nucleus of keratinocytes. Both HSPs were not labeled in the epidermis of the external ear canal skin or normal facial skin, except for significant staining on keratinocytes of hair follicles in facial skin. High density of HSP60 and HSP70 may be induced by the inflammatory reaction and immune responses in the middle ear cavity during the clinical development of cholesteatoma. Induction of HSP60 and HSP70 in cholesteatoma epithelium may also be related to hyperproliferation and active differentiation of basal keratinocytes, which cause the accumulation of keratin debris, a characteristic feature of cholesteatoma. In the nucleus of keratinocytes, HSP70 may act to stabilize p53 protein, which functions as a negative regulator of cellular proliferation and is crucial to apoptosis of keratinocytes. This study demonstrates HSPs in cholesteatoma and suggests important roles for HSPs in the clinical development of cholesteatoma.
Shinoda
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Department of Otolaryngology-Head and Neck Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Huang
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CC
D000328:Adult; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D018834:Chaperonin 60 / Q000032:analysis* / Q000502:physiology; D018424:Cholesteatoma, Middle Ear / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004432:Ear, Middle / Q000378:metabolism / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D016612:Paraffin Embedding; D012967:Sodium Dodecyl Sulfate
D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D012967:Sodium Dodecyl Sulfate