Characterization of the progressive skin disease and inflammatory cell infiltrate in mice with inhibited NF-κB signaling

被引:37
作者
van Hogerlinden, M [1 ]
Rozell, BL
Toftgård, R
Sundberg, JP
机构
[1] Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden
[2] Huddinge Univ Hosp, Dept Clin Pathol & Cytol, S-14186 Huddinge, Sweden
[3] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
I kappa B; inflammation; mice; NF-kappa B; skin neoplasms; transgenic;
D O I
10.1111/j.0022-202X.2004.22706.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
A growth inhibitory role in skin development for the NF-kappaB proteins has been established in recent years. We have previously shown that inhibition of NF-kappaB by overexpression of degradation-resistant IkappaB-alpha in the skin results in the development of squamous cell carcinomas (SCC). In this paper, we characterize the progressive skin disease leading to cancer development in mice with inhibited NF-kappaB signaling in the skin. Increased proliferation and a strong inflammatory response were evident in transgenic skin. A mixed inflammatory cell infiltrate dominated by polymorphonuclear leukocytes was observed in concurrence with an upregulation of the proinflammatory cytokine tumor necrosis factor-alpha. This genetically engineered mouse mutation may be a useful tool to test the efficacy of cytokine therapies for SCC in the future.
引用
收藏
页码:101 / 108
页数:8
相关论文
共 40 条
[1]   Tumor necrosis factor or tumor promoting factor? [J].
Balkwill, F .
CYTOKINE & GROWTH FACTOR REVIEWS, 2002, 13 (02) :135-141
[2]   The multifaceted murine plasmacytoid dendritic cell [J].
Björck, P .
HUMAN IMMUNOLOGY, 2002, 63 (12) :1094-1102
[3]   CACHEXIA AND GRAFT-VS-HOST-DISEASE-TYPE SKIN CHANGES IN KERATIN PROMOTER-DRIVEN TNF-ALPHA TRANSGENIC MICE [J].
CHENG, J ;
TURKSEN, K ;
YU, QC ;
SCHREIBER, H ;
TENG, M ;
FUCHS, E .
GENES & DEVELOPMENT, 1992, 6 (08) :1444-1456
[4]   Inflammation and cancer [J].
Coussens, LM ;
Werb, Z .
NATURE, 2002, 420 (6917) :860-867
[5]   NF-κB blockade and oncogenic Ras trigger invasive human epidermal neoplasia [J].
Dajee, M ;
Lazarov, M ;
Zhang, JY ;
Cai, T ;
Green, CL ;
Russell, AJ ;
Marinkovich, MP ;
Tao, SY ;
Lin, Q ;
Kubo, Y ;
Khavari, PA .
NATURE, 2003, 421 (6923) :639-643
[6]   X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling [J].
Döffinger, R ;
Smahi, A ;
Bessia, C ;
Geissmann, F ;
Feinberg, J ;
Durandy, A ;
Bodemer, C ;
Kenwrick, S ;
Dupuis-Girod, S ;
Blanche, S ;
Wood, P ;
Rabia, SH ;
Headon, DJ ;
Overbeek, PA ;
Le Deist, F ;
Holland, SM ;
Belani, K ;
Kumararatne, DS ;
Fischer, A ;
Shapiro, R ;
Conley, ME ;
Reimund, E ;
Kalhoff, H ;
Abinun, M ;
Munnich, A ;
Israël, A ;
Courtois, G ;
Casanova, JL .
NATURE GENETICS, 2001, 27 (03) :277-285
[7]   Evaluation of classic architectural criteria in non-mycosis fungoides cutaneous lymphomas [J].
Glusac, EJ ;
Kindel, SE ;
Soslow, RA ;
Smoller, BR .
AMERICAN JOURNAL OF DERMATOPATHOLOGY, 1997, 19 (06) :557-561
[8]   Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation [J].
Hendzel, MJ ;
Wei, Y ;
Mancini, MA ;
VanHooser, A ;
Ranalli, T ;
Brinkley, BR ;
BazettJones, DP ;
Allis, CD .
CHROMOSOMA, 1997, 106 (06) :348-360
[9]   IKKα controls formation of the epidermis independently of NF-κB [J].
Hu, YL ;
Baud, V ;
Oga, T ;
Kim, KII ;
Yoshida, K ;
Karin, M .
NATURE, 2001, 410 (6829) :710-714
[10]   Abnormal morphogenesis but intact IKK activation in mice lacking the IKKα subunit of IκB kinase [J].
Hu, YL ;
Baud, V ;
Delhase, M ;
Zhang, PL ;
Deerinck, T ;
Ellisman, M ;
Johnson, R ;
Karin, M .
SCIENCE, 1999, 284 (5412) :316-320