Characterization of the progressive skin disease and inflammatory cell infiltrate in mice with inhibited NF-kappaB signaling.
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.
van Hogerlinden
Max
M
Department of Bioscience at Novum, Karolinska Institutet, NOVUM, Huddinge, Sweden. max.hogerlinden@cnt.ki.se
Rozell
Barbro Lundh
BL
Toftgård
Rune
R
Sundberg
John P
JP
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D002455:Cell Division; D003872:Dermatitis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020672:I-kappa B Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
D015415:Biomarkers; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha