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House dust mite allergens induce interleukin 33 (IL-33) synthesis and release from keratinocytes via ATP-mediated extracellular signaling
Bibliographic Information
- Published
- 2020-05
- Resource Type
- journal article
- Rights Information
-
- https://www.elsevier.com/tdm/userlicense/1.0/
- https://www.elsevier.com/legal/tdmrep-license
- http://www.elsevier.com/open-access/userlicense/1.0/
- DOI
-
- 10.1016/j.bbadis.2020.165719
- Publisher
- Elsevier BV
Search this article
Description
In atopic diseases, the epithelium releases cytokines and chemokines that initiate skin inflammation. Atopic dermatitis (AD) is characterized by a disrupted epidermal barrier and is triggered or exacerbated by environmental stimuli such as house dust mite (HDM) allergens. The proinflammatory cytokine interleukin 33 (IL-33) plays an important role in the pathogenesis of AD, but how IL-33 production in keratinocytes is elicited by HDM is unknown. To that end, here we stimulated monolayer-cultured human keratinocytes and human living skin equivalents with Dermatophagoides pteronyssinus HDM extract to investigate its effects on IL-33 production from keratinocytes. The HDM extract induced intracellular expression of IL-33 and modulated its processing and maturation, triggering rapid IL-33 release from keratinocytes. Group 1 HDM allergen but not group 2 HDM allergen elicited IL-33 production. An ATP assay of keratinocyte culture supernatants revealed an acute and transient accumulation of extracellular ATP immediately after the HDM extract stimulation. Using the broad-spectrum P2 antagonist suramin, the specific purinergic receptor P2Y2 (P2RY2) antagonist AR-C118925XX, and P2RY2-specific siRNA, we discovered that the HDM extract-induced IL-33 expression was mainly dependent on extracellular ATP/P2Y2 signaling mediated by transactivation of epidermal growth factor receptor, followed by activation of the ERK kinase signaling pathway. Moreover, HDM extract-induced release of 25-kDa IL-33 from the keratinocytes depended on an extracellular ATP/P2 signaling-mediated intracellular Ca
Journal
-
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
-
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1866 (5), 165719-, 2020-05
Elsevier BV
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Keywords
- Keratinocytes
- Primary Cell Culture
- Tetrazoles
- Dermatitis, Atopic
- Receptors, Purinergic P2Y2
- Adenosine Triphosphate
- Piperidines
- Humans
- Antigens, Dermatophagoides
- RNA, Small Interfering
- Furans
- Cells, Cultured
- Skin
- Allergens
- Fibroblasts
- Interleukin-33
- Coculture Techniques
- Immunity, Innate
- Purinergic P2Y Receptor Antagonists
- Extracellular Space
- Signal Transduction
Details 詳細情報について
-
- CRID
- 1361694366522293376
-
- ISSN
- 09254439
-
- PubMed
- 32044300
-
- Article Type
- journal article
-
- Data Source
-
- Crossref
- KAKEN
- OpenAIRE
