IFNα converts IL-22 into a cytokine efficiently activating STAT1 and its downstream targets.

Abstract

Besides their antiviral activity, type I Interferons (IFN) display context-specific immunomodulation. In contrast to long-known IFNα/β, Interleukin (IL)-22 is an anti-bacterial, largely tissue protective cytokine that recently gained attention. Herein, cellular IFNα/IL-22 interactions are investigated. We report that pre-conditioning of epithelial cells with IFNα initiated dramatic changes in IL-22 signaling normally dominated by signal transducer and activator of transcription (STAT)-3. Specifically, by using human DLD1 colon epithelial/carcinoma cells we demonstrate that, upon IFNα, IL-22 converts into a cytokine robustly activating STAT1 and its downstream pro-inflammatory targets CXCL9, CXCL10, and inducible nitric oxide synthase (iNOS). Accordingly, only after IFNα pre-incubation was IL-22-induced STAT1 binding to the CXCL10 promoter detectable. Using the viral mimic polyinosinic:polycytidylic acid and the IFNα/β antagonist B18R we furthermore demonstrate the capability of endogenous IFN to promote IL-22-induced STAT1 activation and expression of CXCL10. IL-22-induced STAT1 activation subsequent to IFNα priming became likewise apparent in human Caco2 colon epithelial/carcinoma cells, HepG2 hepatoma cells, and primary keratinocytes. Current observations may relate to characteristics of IFNα/β in clinical therapy and expose margins of tissue protection by IL-22 application.

• Authors: Malte Bachmann, Solongo Ulziibat, Lorena Härdle, Josef Pfeilschifter, Heiko Mühl
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 85 Issue 3 Pg. 396-403 (Feb 01 2013) ISSN: 1873-2968 [Electronic] England
• PMID: 23153456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Interferon-alpha
• Interleukins
• RNA, Messenger
• Receptors, Interleukin
• STAT1 Transcription Factor
• STAT1 protein, human
• interleukin-22 receptor

Topics

• Cell Line, Tumor
• Chromatin Immunoprecipitation
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Regulation (physiology)
• Humans
• Interferon-alpha (pharmacology)
• Interleukins (genetics, metabolism)
• Keratinocytes (metabolism)
• Promoter Regions, Genetic
• RNA, Messenger (genetics, metabolism)
• Receptors, Interleukin (genetics, metabolism)
• STAT1 Transcription Factor (genetics, metabolism)
• Time Factors
• Interleukin-22