ASK1 promotes the contact hypersensitivity response through IL-17 production
| Autor: | Junya Mizukami, Takehiro Sato, Dominique Swinnen, Thomas Rueckle, Kohsuke Takeda, Ryoji Tsuboi, Hidenori Ichijo, Hong Ji, Montserrat Camps |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_treatment Dermatitis Contact MAP Kinase Kinase Kinase 5 p38 Mitogen-Activated Protein Kinases Article Interferon-gamma Mice hemic and lymphatic diseases medicine Animals Humans ASK1 Interferon gamma skin and connective tissue diseases Allergic contact dermatitis Sensitization Mice Knockout Multidisciplinary integumentary system business.industry Interleukin-17 medicine.disease Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Cytokine HEK293 Cells Immunology Dinitrofluorobenzene Interleukin 17 business Contact dermatitis Hapten medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Contact hypersensitivity (CHS) is a form of delayed-type hypersensitivity triggered by the response to reactive haptens (sensitization) and subsequent challenge (elicitation). Here, we show that ASK1 promotes CHS and that suppression of ASK1 during the elicitation phase is sufficient to attenuate CHS. ASK1 knockout (KO) mice exhibited impaired 2,4-dinitrofluorobenzene (DNFB)-induced CHS. The suppression of ASK1 activity during the elicitation phase through a chemical genetic approach or a specific inhibitory compound significantly reduced the CHS response to a level similar to that observed in ASK1 KO mice. The reduced response was concomitant with the strong inhibition of production of IL-17, a cytokine that plays an important role in CHS and other inflammatory diseases, from sensitized lymph node cells. These results suggest that ASK1 is relevant to the overall CHS response during the elicitation phase and that ASK1 may be a promising therapeutic target for allergic contact dermatitis and other IL-17-related inflammatory diseases. Scientific Reports, 4, 4714; 2014 |
| Databáze: | OpenAIRE |
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