Document Detail


Discordant expression of Bcl-x and Bcl-2 by keratinocytes in vitro and psoriatic keratinocytes in vivo.
MedLine Citation:
PMID:  7747803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis is a required event in maintaining kinetic homeostasis within continually renewing tissues such as skin. However, no systematic study of the apoptotic process in epidermal keratinocytes of the skin has been performed. In this report, we examined the expression of proteins associated with promoting (Fas) or preventing (Bcl-2, Bcl-x, CD40) apoptosis in the normal, psoriatic, and malignant keratinocyte. Immunohistochemical staining and flow cytometry analysis revealed that normal cultured keratinocytes express low levels of Fas, CD40, and Bcl-x that was enhanced by cytokines including gamma-interferon (IFN-gamma) and a phorbol ester tumor promoter, TPA. Only faint Bcl-2 staining was detected in cultured keratinocytes exposed to IFN-gamma and TPA compared with the prominent expression of Bcl-x. Biopsies of normal skin, psoriatic plaques, and basal cell carcinomas were examined to extend the in vitro observations. Immunohistochemical staining revealed that while keratinocytes in normal epithelium express low to absent levels of Fas and Bcl-x, psoriatic keratinocytes expressed significantly higher levels of Fas and Bcl-x. In contrast, malignant keratinocytes in basal cell carcinomas expressed high levels of Bcl-2, but minimal Bcl-x, and no Fas. Immunoblot analysis revealed that the long form of Bcl-x (Bcl-xI), which prevents apoptosis in lymphocytes, is expressed by cultured keratinocytes and psoriatic plaque keratinocytes. We conclude that normal cytokine-activated keratinocytes can express an apoptotic (Fas) and an anti-apoptotic protein (Bcl-x). The overexpression of Bcl-x in psoriasis, or Bcl-2 in basal cell carcinomas, may contribute to the longevity of these cells by blocking the normal apoptotic process involved in the terminal differentiation program of epidermal keratinocytes.
Authors:
T Wrone-Smith; T Johnson; B Nelson; L H Boise; C B Thompson; G Núñez; B J Nickoloff
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  146     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  1995 May 
Date Detail:
Created Date:  1995-06-15     Completed Date:  1995-06-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1079-88     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cells, Cultured
Flow Cytometry
Fluorescent Antibody Technique
Humans
Immunoblotting
Immunoenzyme Techniques
Keratinocytes / metabolism*
Proto-Oncogene Proteins / biosynthesis*
Proto-Oncogene Proteins c-bcl-2
Psoriasis / metabolism*
bcl-X Protein
Grant Support
ID/Acronym/Agency:
AR 38957/AR/NIAMS NIH HHS; AR 40065/AR/NIAMS NIH HHS; AR 40488/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/BCL2L1 protein, human; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-X Protein
Comments/Corrections

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