The UV response of the skin: a review of the MAPK, NFkappaB and TNFalpha signal transduction pathways.
The sun emits different types of ultraviolet (UV) light. Our skin is a natural target of UV radiation which is involved in vitamin D3 production in our body. UV radiation at high doses is an environmental carcinogen which can elicit skin damage as well as inducing skin cancer. It can mediate inflammatory and immunological reactions through activation of receptors, DNA/RNA damage and production of reactive oxygen species. It is also involved in the release of pro-inflammatory cytokines, of which TNFalpha has been implicated in tumorigenic activities. In order to mediate its effects, UV radiation is known to activate multiple signalling cascades such as the p38 MAPK, Jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and NFkappaB pathways in skin cells. The role each of these pathways plays in mediating the release of cytokines such as TNFalpha remains to be fully characterized. Once the function of these pathways is known, this information may provide for the formulation of therapy which will prevent the release of immunosuppressive cytokines resulting in a reduction in skin cancer formation.
Muthusamy
Visalini
V
School of Medical Sciences, RMIT University, PO Box 71, Bundoora, VIC 3083, Australia. visalini.muthusamy@rmit.edu.au
Piva
Terrence J
TJ
D000818:Animals; D002762:Cholecalciferol / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects; D015195:Drug Design; D006801:Humans; D007113:Immunity, Innate / Q000528:radiation effects; D007165:Immunosuppression Therapy; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology / Q000528:radiation effects*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D048051:p38 Mitogen-Activated Protein Kinases