ULTRAVIOLET-B-INDUCED APOPTOSIS OF KERATINOCYTES - EVIDENCE FOR PARTIAL INVOLVEMENT OF TUMOR-NECROSIS-FACTOR-ALPHA IN THE FORMATION OF SUNBURN CELLS

被引:244
作者
SCHWARZ, A [1 ]
BHARDWAJ, R [1 ]
ARAGANE, Y [1 ]
MAHNKE, K [1 ]
RIEMANN, H [1 ]
METZE, D [1 ]
LUGER, TA [1 ]
SCHWARZ, T [1 ]
机构
[1] UNIV MUNSTER, DEPT DERMATOL, LUDWIG BOLTZMANN INST CELL BIOL & IMMUNOBIOL SKIN, D-48149 MUNSTER, GERMANY
关键词
D O I
10.1111/1523-1747.ep12606202
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Irradiation with ultraviolet (UV) B radiation results in the formation of apoptotic keratinocytes called sunburn cells. Recently, it was demonstrated that keratinocytes can release tumor necrosis factor-alpha (TNF-alpha), which is known to cause apoptosis in particular cells. In addition, it has been shown that UVB light induces the release of TNF-alpha by keratinocytes and that keratinocytes express the 55-kD receptor for TNF-alpha. Therefore, we investigated whether TNF-alpha is involved in UV-induced apoptosis of keratinocytes. Normal human keratinocytes and HaCaT cells were exposed to UVB light, and apoptosis was examined by nick translation evaluated by fluorescence-activated cell sorter analysis. UVB induced apoptosis in a dose-dependent manner, which was confirmed by electron microscopy. Addition of a polyclonal antibody directed against human TNF-alpha immediately after UVB exposure was able to reduce DNA fragmentation. However, it was not possible to rescue all cells from apoptosis. To prove whether TNF-alpha is also involved in vivo in UVB-induced apoptosis of keratinocytes, Balb/c mice were exposed to UVB on their abdomens, skin biopsies were performed 24 h later, and sunburn cells were counted. A single dose of 2000 J/m(2) caused a significant induction of sunburn cells. Subcutaneous injection of a polyclonal antibody directed against murine TNF-alpha immediately after UVB treatment resulted in a significant but incomplete reduction of sunburn cells, whereas injection of a rabbit IgG as a control had no effect. In both the in vitro and in vivo systems, application of recombinant TNF-alpha alone either to untreated keratinocytes or into normal murine skin did not induce sunburn cells. Thus, these data demonstrate that TNF-alpha is involved in UVB-induced apoptosis, but by itself is not able to induce sunburn cells. This further supports the notion that UVB-induced apoptosis of keratinocytes is a multifactorial event.
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页码:922 / 927
页数:6
相关论文
共 34 条
[21]   INDUCTION OF APOPTOTIC DNA-DAMAGE AND CELL-DEATH BY ACTIVATION OF THE SPHINGOMYELIN PATHWAY [J].
JARVIS, WD ;
KOLESNICK, RN ;
FORNARI, FA ;
TRAYLOR, RS ;
GEWIRTZ, DA ;
GRANT, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (01) :73-77
[22]   LYSOSOMES AND REACTIONS OF SKIN TO ULTRAVIOLET RADIATION [J].
JOHNSON, BE ;
DANIELS, F .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1969, 53 (02) :85-+
[23]  
Kerr JF, 1991, APOPTOSIS MOL BASIS
[24]   HUMAN KERATINOCYTES ARE A SOURCE FOR TUMOR-NECROSIS-FACTOR-ALPHA - EVIDENCE FOR SYNTHESIS AND RELEASE UPON STIMULATION WITH ENDOTOXIN OR ULTRAVIOLET-LIGHT [J].
KOCK, A ;
SCHWARZ, T ;
KIRNBAUER, R ;
URBANSKI, A ;
PERRY, P ;
ANSEL, JC ;
LUGER, TA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (06) :1609-1614
[25]   ACTIVATION OF PROGRAMMED CELL-DEATH BY RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR PLUS TOPOISOMERASE II-TARGETED DRUGS IN L929 TUMOR-CELLS [J].
KYPRIANOU, N ;
ALEXANDER, RB ;
ISAACS, JT .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1991, 83 (05) :346-350
[26]   CYTOTOXIC MECHANISM OF TUMOR-NECROSIS-FACTOR-ALPHA [J].
LARRICK, JW ;
WRIGHT, SC .
FASEB JOURNAL, 1990, 4 (14) :3215-3223
[27]   INDUCTION OF APOPTOSIS (PROGRAMMED CELL-DEATH) IN TUMOR-CELL LINES BY WIDELY DIVERGING STIMULI [J].
LENNON, SV ;
MARTIN, SJ ;
COTTER, TG .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1990, 18 (02) :343-345
[28]   ULTRAVIOLET-B IRRADIATION OF HUMAN LEUKEMIA HL-60 CELLS-INVITRO INDUCES APOPTOSIS [J].
MARTIN, SJ ;
COTTER, TG .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1991, 59 (04) :1001-1016
[29]   SUNBURN CELL-FORMATION IS PREVENTED BY SCAVENGING OXYGEN INTERMEDIATES [J].
MIYACHI, Y ;
HORIO, T ;
IMAMURA, S .
CLINICAL AND EXPERIMENTAL DERMATOLOGY, 1983, 8 (03) :305-310
[30]   PROGRAMMED CELL-DEATH, APOPTOSIS AND KILLER GENES [J].
SCHWARTZ, LM ;
OSBORNE, BA .
IMMUNOLOGY TODAY, 1993, 14 (12) :582-590