Transglutaminase 2 mediates UV-induced skin inflammation by enhancing inflammatory cytokine production
| Autor: | Eui Man Jeong, Young Hoon Son, Ji Woong Shin, Won Jong Lee, Hyo Jun Kim, Dong Hun Lee, Mee ae Kwon, Ah Young Hong, Jin Haeng Lee, In Gyu Kim, Seok Jin Lee, Jin Hee Kim, Ki Baek Lee, Hee Won Bae |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Ultraviolet Rays Tissue transglutaminase medicine.medical_treatment Photoaging Immunology Apoptosis Inflammation Skin Diseases Proinflammatory cytokine Mice 03 medical and health sciences Cellular and Molecular Neuroscience GTP-Binding Proteins medicine Animals Humans Protein Glutamine gamma Glutamyltransferase 2 Skin Mice Knockout Transglutaminases Phospholipase C biology Chemistry Cell Biology medicine.disease Cell biology HaCaT 030104 developmental biology Cytokine Gene Knockdown Techniques biology.protein Cytokines Original Article Female Signal transduction medicine.symptom Signal Transduction |
| Zdroj: | Cell Death & Disease CELL DEATH & DISEASE(8) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2017.550 |
| Popis: | UV irradiation elicits acute inflammation in the skin by increasing proinflammatory cytokine production in keratinocytes. However, the downstream protein target(s) that link UV radiation to the activation of signaling pathways responsible for cytokine expression have not been fully elucidated. In this study, we report a novel role of transglutaminase 2 (TG2), a member of the TG enzyme family whose activities are critical for cornified envelope formation, in mediating UV-induced inflammation. Our results showed that TG2-deficient mice exhibited reduced inflammatory responses to UV irradiation, including reduced erythema, edema, dilation of blood vessels, inflammatory cell infiltration, and levels of inflammatory cytokines. Using primary mouse keratinocytes and HaCaT cells, we found that UV irradiation-induced cytokine production by activating TG2, but not by upregulating TG2 expression, and that ER calcium release triggered by the UV-induced activation of phospholipase C was required for TG2 activation. Moreover, TG2 activity enhanced p65 phosphorylation, leading to an increase in NF-κB transcriptional activity. These results indicate that TG2 is a critical mediator of cytokine expression in the UV-induced inflammatory response of keratinocytes, and suggest that TG2 inhibition might be useful for preventing UV-related skin disorders, such as photoaging and skin cancer caused by chronic UV exposure. |
| Databáze: | OpenAIRE |
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