This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wrone-Smith, T. Articles by Nickoloff, B. J. Search for Related Content PubMed PubMed Citation Articles by Wrone-Smith, T. Articles by Nickoloff, B. J.

American Journal of Pathology, Vol 146, 1079-1088, Copyright © 1995 by American Society for Investigative Pathology

REGULAR ARTICLES

Discordant expression of Bcl-x and Bcl-2 by keratinocytes in vitro and psoriatic keratinocytes in vivo

T Wrone-Smith, T Johnson, B Nelson, LH Boise, CB Thompson, G Nunez and BJ Nickoloff
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.

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.

This article has been cited by other articles:

				A. Gilhar, R. Yaniv, B. Assy, S. Serafimovich, Y. Ullmann, and R. S. Kalish Fas Pulls the Trigger on Psoriasis Am. J. Pathol., January 1, 2006; 168(1): 170 - 175. [Abstract] [Full Text] [PDF]

				E. REEFMAN, P. C. LIMBURG, C. G. M. KALLENBERG, and M. BIJL Apoptosis in Human Skin: Role in Pathogenesis of Various Diseases and Relevance for Therapy Ann. N.Y. Acad. Sci., June 1, 2005; 1051(1): 52 - 63. [Abstract] [Full Text] [PDF]

				S. Weijzen, M. P. Velders, A. G. Elmishad, P. E. Bacon, J. R. Panella, B. J. Nickoloff, L. Miele, and W. M. Kast The Notch Ligand Jagged-1 Is Able to Induce Maturation of Monocyte-Derived Human Dendritic Cells J. Immunol., October 15, 2002; 169(8): 4273 - 4278. [Abstract] [Full Text] [PDF]

				R. Ruckert, K. Asadullah, M. Seifert, V. M. Budagian, R. Arnold, C. Trombotto, R. Paus, and S. Bulfone-Paus Inhibition of Keratinocyte Apoptosis by IL-15: A New Parameter in the Pathogenesis of Psoriasis? J. Immunol., August 15, 2000; 165(4): 2240 - 2250. [Abstract] [Full Text] [PDF]

				S.-H. CHEN, I. ARANY, N. APISARNTHANARAX, S. RAJARAMAN, S. K. TYRING, T. HORIKOSHI, H. BRYSK, and M. M. BRYSK Response of keratinocytes from normal and psoriatic epidermis to interferon-{gamma} differs in the expression of zinc-{alpha}2-glycoprotein and cathepsin D FASEB J, March 1, 2000; 14(3): 565 - 571. [Abstract] [Full Text]

				P. Monti, A. Inga, A. Aprile, P. Campomenosi, P. Menichini, L. Ottaggio, S. Viaggi, G. Ghigliotti, A. Abbondandolo, and G. Fronza p53 mutations experimentally induced by 8-methoxypsoralen plus UVA (PUVA) differ from those found in human skin cancers in PUVA-treated patients Mutagenesis, March 1, 2000; 15(2): 127 - 132. [Abstract] [Full Text] [PDF]

				J.-Z. Qin, V. Chaturvedi, M. F. Denning, D. Choubey, M. O. Diaz, and B. J. Nickoloff Role of NF-kappa B in the Apoptotic-resistant Phenotype of Keratinocytes J. Biol. Chem., December 31, 1999; 274(53): 37957 - 37964. [Abstract] [Full Text] [PDF]

				V. Chaturvedi, J.-Z. Qin, M. F. Denning, D. Choubey, M. O. Diaz, and B. J. Nickoloff Apoptosis in Proliferating, Senescent, and Immortalized Keratinocytes J. Biol. Chem., August 13, 1999; 274(33): 23358 - 23367. [Abstract] [Full Text] [PDF]

				K. Hong, A. Chu, B. R. Ludviksson, E. L. Berg, and R. O. Ehrhardt IL-12, Independently of IFN-{gamma}, Plays a Crucial Role in the Pathogenesis of a Murine Psoriasis-Like Skin Disorder J. Immunol., June 15, 1999; 162(12): 7480 - 7491. [Abstract] [Full Text] [PDF]

				U. Rodeck, M. Jost, J. DuHadaway, C. Kari, P. J. Jensen, B. Risse, and D. L. Ewert Regulation of Bcl-xL expression in human keratinocytes by cell-substratum adhesion and the epidermal growth factor receptor PNAS, May 13, 1997; 94(10): 5067 - 5072. [Abstract] [Full Text] [PDF]