The Double-Stranded RNA Analogue Polyinosinic-Polycytidylic Acid Induces Keratinocyte Pyroptosis and Release of IL-36γ
| Autor: | Katelynn A. Milora, Liselotte E. Jensen, Li-Hua Lian, Katherine K. Manupipatpong |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Keratinocytes
Transcription Genetic Interleukin-1beta Dermatology Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Interleukin-1alpha Protein biosynthesis Extracellular medicine Humans RNA Messenger Molecular Biology Cells Cultured 030304 developmental biology Caspase 7 0303 health sciences Innate immune system Cell Death biology Caspase 3 Caspase 1 Pyroptosis Cell Biology Molecular biology 3. Good health Cell biology Poly I-C medicine.anatomical_structure chemistry Polyinosinic:polycytidylic acid biology.protein Keratinocyte Flagellin Intracellular Interleukin-1 Signal Transduction 030215 immunology |
| Zdroj: | Journal of Investigative Dermatology. 132:1346-1353 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2011.482 |
| Popis: | IL-36 is the common name for the three IL-1 family members IL-36α, IL-36β, and IL-36γ, formerly known as IL-1F6, IL-1F8, and IL-1F9, respectively. IL-36 appears to have pro-inflammatory activities; however, the physiological function of these cytokines remains unknown. Expression of IL-36 by keratinocytes implies its possible involvement in innate immune responses in the skin. We observed that, of the three IL-36 isoforms, human keratinocytes express high levels of IL-36γ. IL-36γ mRNA expression was dramatically induced by the Toll-like receptor ligands polyinosinic-polycytidylic acid (poly(I:C)) and flagellin. Surprisingly, the IL-36γ protein was released by cells treated with poly(I:C), but remained intracellular in cells treated with flagellin only. poly(I:C), but not flagellin, induced cell death and caspase-3/7 activation. Inhibition of caspase-3/7 and caspase-1 blocked extracellular release of IL-36γ from poly(I:C)-treated cells. Furthermore, caspase-1 inhibition prevented poly(I:C)-induced caspase-3/7 activation. Interestingly, transcription of the gene IL36G was dependent on caspase-1, but not caspase-3/7, activation. This demonstrates that the pathways leading to IL36G transcription and caspase-3/7 activation branch after caspase-1. This divergence of the pathways allows the cells to enter a state of de novo protein synthesis before committing to pyroptosis. Overall, our observations suggest that IL-36γ may be an alarmin that signals the cause, e.g., viral infection, of cell death. |
| Databáze: | OpenAIRE |
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