Low Interleukin-22 Binding Protein Is Associated With High Mortality in Alcoholic Hepatitis and Modulates Interleukin-22 Receptor Expression
| Autor: | Sidsel Støy, Kristoffer T.G. Rigbolt, Ewa Terczyńska-Dyla, Tea Lund Laursen, Nils E. Magnusson, Stephen Hamilton-Dutoit, Oliviero Riggio, Peter Lykke Eriksen, Bent Deleuran, Emilie Glavind, Frank Viborg Mortensen, Hendrik Vilstrup, Thomas Damgaard Sandahl, Sanne Skovgård Veidal |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Biopsy Receptor expression Primary Cell Culture Alcoholic hepatitis Article Interleukin 22 Pathogenesis 03 medical and health sciences Liver disease 0302 clinical medicine Internal medicine medicine Humans Prospective Studies Hepatitis Hepatitis Alcoholic business.industry Interleukins Gastroenterology Interleukin Hep G2 Cells Receptors Interleukin Middle Aged medicine.disease Healthy Volunteers Recombinant Proteins Liver regeneration Culture Media Up-Regulation Endocrinology Liver Case-Control Studies 030220 oncology & carcinogenesis Hepatocytes Female 030211 gastroenterology & hepatology business Follow-Up Studies Signal Transduction |
| Zdroj: | Støy, S, Laursen, T L, Glavind, E, Eriksen, P L, Terczynska-Dyla, E, Magnusson, N E, Hamilton-Dutoit, S, Mortensen, F V, Veidal, S S, Rigbolt, K, Riggio, O, Deleuran, B, Vilstrup, H & Sandahl, T D 2020, ' Low Interleukin-22 Binding Protein Is Associated With High Mortality in Alcoholic Hepatitis and Modulates Interleukin-22 Receptor Expression ', Clinical and Translational Gastroenterology, vol. 11, no. 8, pp. e00197 . https://doi.org/10.14309/ctg.0000000000000197 Clinical and Translational Gastroenterology |
| DOI: | 10.14309/ctg.0000000000000197 |
| Popis: | INTRODUCTION: In alcoholic hepatitis (AH), high interleukin (IL)-22 production is associated with disease improvement, purportedly through enhanced infection resistance and liver regeneration. IL-22 binding protein (BP) binds and antagonizes IL-22 bioactivity, but data on IL-22BP in liver disease suggest a complex interplay. Despite the scarcity of human data, IL-22 is in clinical trial as treatment of AH. We, therefore, in patients with AH, described the IL-22 system focusing on IL-22BP and associations with disease course, and mechanistically pursued the human associations in vitro.METHODS: We prospectively studied 41 consecutive patients with AH at diagnosis, days 7 and 90, and followed them for up to 1 year. We measured IL-22 pathway proteins in liver biopsies and blood and investigated IL-22BP effects on IL-22 in hepatocyte cultures.RESULTS: IL-22BP was produced in the gut and was identifiable in the patients with AH' livers. Plasma IL-22BP was only 50% of controls and the IL-22/IL-22BP ratio thus elevated. Consistently, IL-22-inducible genes were upregulated in AH livers at diagnosis. Low plasma IL-22BP was closely associated with high 1-year mortality. In vitro, IL-22 stimulation reduced IL-22 receptor (R) expression, but coincubation with IL-22BP sustained IL-22R expression. In the AH livers, IL-22R mRNA expression was similar to healthy livers, although IL-22R liver protein was higher at diagnosis.DISCUSSION: Plasma IL-22BP was associated with an adverse disease course, possibly because its low level reduces IL-22R expression so that IL-22 bioactivity was reduced. This suggests the IL-BP interplay to be central in AH pathogenesis, and in future treatment trials (see Visual abstract, Supplementary Digital Content 5, http://links.lww.com/CTG/A338). |
| Databáze: | OpenAIRE |
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