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Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis

1999; Volume: 188; Issue: 1 Linguagem: Inglês

10.1002/(sici)1096-9896(199905)188

1096-9896

José L. Pablos, Bego�a Santiago, María Galindo, Patrícia Carreira, Claudio Ballestı́n, Juan J. Gómez‐Reino,

Skin Diseases and Diabetes

The Journal of PathologyVolume 188, Issue 1 p. 63-68 Original Paper Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis Jose L. Pablos, Corresponding Author Jose L. Pablos [email protected] Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainServico de Reumatologia, Hospital 12 de Octubre, 28041 Madrid, SpainSearch for more papers by this authorBegoña Santiago, Begoña Santiago Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorMaria Galindo, Maria Galindo Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorPatricia E. Carreira, Patricia E. Carreira Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorClaudio Ballestin, Claudio Ballestin Servicio de Anatomía Patológica, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorJuan J. Gomez-Reino, Juan J. Gomez-Reino Servicio de Reumatología, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, SpainSearch for more papers by this author Jose L. Pablos, Corresponding Author Jose L. Pablos [email protected] Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainServico de Reumatologia, Hospital 12 de Octubre, 28041 Madrid, SpainSearch for more papers by this authorBegoña Santiago, Begoña Santiago Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorMaria Galindo, Maria Galindo Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorPatricia E. Carreira, Patricia E. Carreira Servicio de Reumatología, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorClaudio Ballestin, Claudio Ballestin Servicio de Anatomía Patológica, Hospital 12 de Octubre, Madrid, SpainSearch for more papers by this authorJuan J. Gomez-Reino, Juan J. Gomez-Reino Servicio de Reumatología, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, SpainSearch for more papers by this author First published: 06 December 1999 https://doi.org/10.1002/(SICI)1096-9896(199905)188:1 3.0.CO;2-ECitations: 54AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Keratinocyte apoptosis may be induced by ultraviolet-B radiation and represents a potential source of fragmented autoantigens in autoimmune diseases. This study investigates whether excessive keratinocyte apoptosis occurs in the skin lesions of cutaneous lupus (CLE) and dermatomyositis (DM) and the potential mechanisms responsible for this phenomenon. Skin biopsies have been studied from 19 patients with CLE and DM, eight with scleroderma, and five healthy controls. Apoptosis was detected by in situ end-labelling of fragmented DNA. The expression of Bcl-2, PCNA, p53, and Ki-67 proteins was studied by immunohistochemistry. In DM and CLE skin, the number of apoptotic keratinocytes was significantly increased (p=0·008) compared with normal skin. In both diseases, a large accumulation of apoptotic keratinocytes and apoptotic bodies was present in the disrupted basal zone. Unlike normal skin, a large number of keratinocytes, particularly those morphologically apoptotic, expressed p53 protein. A significant increase in the number of proliferating Ki-67 positive (p=0·0007) and PCNA-positive (p=0·0008) nuclei was also observed. In both CLE and DM, exaggerated and inappropriate keratinocyte apoptosis occurs. It is associated with increased expression of p53 and PCNA. This suggests that normal solar radiation alone or in combination with additional local factors induces DNA damage and excessive keratinocyte apoptosis in these autoimmune diseases of the skin. Apoptosis can mediate the severe epidermal lesions observed in both diseases and the release of fragmented autoantigens into the dermis. Copyright © 1999 John Wiley & Sons, Ltd. REFERENCES 1 Provost TT, Watson R. Pathogenesis of cutaneous manifestations of lupus erythematosus. In: DJ Wallace, D Hahn, eds. Dubois' Lupus Erythematosus. 4th edn. Philadelphia: Lea & Febiger, 1993: 279–301. Google Scholar 2 Bradley WG, Tandan R. Inflammatory diseases of muscle. In: WN Kelley, ED Harris S Ruddy, CB Sledge, eds. Textbook of Rheumatology. 3rd edn. Philadelphia: WB Saunders, 1989: 1263–1287. Google Scholar 3 Andrews BS, Schenk A, Barr R, Friou G, Mirick G, Ross P. 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