TAK1 regulates reactive oxygen species and cell death in keratinocytes, which is essential for skin integrity
| Autor: | Kunihiro Matsumoto, Sho Morioka, Emily Omori, Jun Ninomiya-Tsuji |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Keratinocytes
Programmed cell death Proto-Oncogene Proteins c-jun Transgene Inflammation Mice Transgenic Biology medicine.disease_cause Biochemistry Models Biological Antioxidants Mice medicine Animals Molecular Biology Skin chemistry.chemical_classification Reactive oxygen species Mechanisms of Signal Transduction NF-kappa B Cytochromes c Cell Biology NFKB1 MAP Kinase Kinase Kinases Cell biology Oxidative Stress chemistry Gene Expression Regulation Ectopic expression Tumor necrosis factor alpha medicine.symptom Reactive Oxygen Species Oxidative stress |
| Zdroj: | The Journal of biological chemistry. 283(38) |
| ISSN: | 0021-9258 |
| Popis: | Mice with a keratinocyte-specific deletion of Tak1 exhibit severe skin inflammation due to hypersensitivity to tumor necrosis factor (TNF) killing. Here we have examined the mechanisms underlying this hypersensitivity. We found that TAK1 deficiency up-regulates reactive oxygen species (ROS) resulting in cell death upon TNF or oxidative stress challenge. Because blockade of NF-κB did not increase ROS or did not sensitize cells to oxidative stress in keratinocytes TAK1 regulates ROS mainly through the mechanisms other than those mediated by NF-κB. We found that c-Jun was decreased in TAK1-deficient keratinocytes and that ectopic expression of c-Jun could partially inhibit TNF-induced increase of ROS and cell death. Finally, we show that, in an in vivo setting, the antioxidant treatment could reduce an inflammatory condition in keratinocyte-specific Tak1 deletion mice. Thus, TAK1 regulates ROS partially through c-Jun, which is important for preventing ROS-induced skin inflammation. |
| Databáze: | OpenAIRE |
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