![]() There is an ongoing debate as to whether allergic disease is a risk factor for cancer or whether it is protective, with recent studies indicating that the relationship is complex and site specific ( Arana et al., 2010 Wedgeworth et al., 2011 Hwang et al., 2012). propose that the immune reaction caused by this exaggerated response could help to prevent tumour formation by eliminating tumour-forming cells in the skin. This response comprised the production of higher levels of various proteins that are involved in communications between skin cells and the immune system. The knockout mice and the wild-type mice responded to DMBA in the same way however, the knockout mice showed an exaggerated response to TPA, including a strong inflammatory reaction. then compared how the mice responded to DMBA or TPA alone. This shows that the mutations that cause the epidermal barrier defects in knockout mice also protect them against the tumours caused by the combined effects of DMBA and TPA.Ĭipolat et al. Overall, the average number of benign tumours per mouse was six times higher in the wild-type mice. After about 16 weeks almost all of the wild-type mice had at least one benign tumour, whereas half of the knockout mice had no tumours. Knockout mice and wild-type mice were treated with two chemicals: DMBA, which causes mutations in a gene called HRas, and TPA, which promotes the formation of tumours from cells that contain HRas mutations. have investigated whether defects in the epidermal barrier protect against skin cancer. These ‘triple knockout mice’ have a defective epidermal barrier and altered levels of immune T-cells in the skin. ![]() Genetically engineered mice that are lacking three proteins that are involved in the formation of the cornified envelope-the protective layer that replaces the normal plasma membrane in the cells of the outermost skin layers-can be used to study atopic dermatitis. However, it is difficult to know if this reduction is due to the atopic dermatitis itself or to the drugs used to treat this allergy. There is some evidence from epidemiological studies that patients with certain allergies might be protected against cancer and, in particular, that the allergic skin condition atopic dermatitis is associated with reduced levels of various skin cancers. Skin cancer is a common and growing problem-according to the World Health Organization, skin cancers account for one in every three cancers diagnosed world wide. We conclude that atopy is protective against skin cancer in our experimental model and that the mechanism involves keratinocytes communicating with cells of the immune system via signalling elements that normally protect against environmental assaults. The exacerbated TPA response could be normalised by blocking TSLP or the immunoreceptor NKG2D but not CD4+ T cells. The DMBA response was normal, but EPI−/− skin exhibited an exaggerated atopic response to TPA, characterised by abnormal epidermal differentiation, a complex immune infiltrate and elevated serum thymic stromal lymphopoietin (TSLP). ![]() EPI−/− mice were highly resistant to developing benign tumours when treated with 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). To test whether this influences tumour formation, we chemically induced tumours in EPI−/− mice, which lack three barrier proteins-Envoplakin, Periplakin, and Involucrin. Atopic dermatitis can result from loss of structural proteins in the outermost epidermal layers, leading to a defective epidermal barrier.
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