Therapeutic elimination of the type 1 interferon receptor for treating psoriatic skin inflammation
Autor: | Victoria P. Werth, Darren P. Baker, Hallgeir Rui, Serge Y. Fuchs, Christine Marshall, Michael D. Gober, Kanstantsin V. Katlinski, John T. Seykora, Meena R. Sharma, Xiaoping Yang, Jun Gui |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Keratinocytes Male Chemokine Down-Regulation Inflammation Dermatology Receptor Interferon alpha-beta Biology Biochemistry Ultraviolet therapy Article Proinflammatory cytokine Cell Line 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Piperidines Psoriasis medicine Animals Humans Molecular Biology Quinazolinones Skin Mice Knockout Halofuginone Ubiquitination Cell Biology medicine.disease 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Immunology biology.protein Cytokines Ultraviolet Therapy medicine.symptom Signal transduction Chemokines medicine.drug Signal Transduction |
Popis: | Phototherapy with ultraviolet (UV) light is a standard treatment for psoriasis, yet the mechanisms underlying the therapeutic effects are not well understood. Studies in human and mouse keratinocytes and in the skin tissues from human patients and mice showed that UV treatment triggers ubiquitination and downregulation of the type I interferon (IFN) receptor chain IFNAR1, leading to suppression of IFN signaling and an ensuing decrease in the expression of inflammatory cytokines and chemokines. The severity of imiquimod-induced psoriasiform inflammation was greatly exacerbated in skin of mice deficient in IFNAR1 ubiquitination (Ifnar1SA). Furthermore, these mice did not benefit from UV phototherapy. Pharmacologic induction of IFNAR1 ubiquitination and degradation by an antiprotozoal agent halofuginone also relieved psoriasiform inflammation in wild type but not in Ifnar1SA mice. These data identify downregulation of IFNAR1 by UV as a major mechanism of the UV therapeutic effects against the psoriatic inflammation and provide a proof of principle for future development of agents capable of inducing IFNAR1 ubiquitination and downregulation for the treatment of psoriasis. |
Databáze: | OpenAIRE |
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