The murine liver is a potential target organ for IL-19, IL-20 and IL-24: Type I Interferons and LPS regulate the expression of IL-20R2

• Published in: Journal of hepatology Vol. 46; no. 2; pp. 257 - 265
• Main Authors: Wegenka, Ursula Maria, Dikopoulos, Nektarios, Reimann, Jörg, Adler, Guido, Wahl, Christian
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01-02-2007; Elsevier
• Subjects: Acute-Phase Proteins - analysis; Animals; Biological and medical sciences; Cytokines - blood; Cytokines - genetics; Cytokines - metabolism; Endotoxin shock; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; IFNβ; IL-19; IL-20; IL-20R2; IL-22; IL-24; Interferon Type I - physiology; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukins - blood; Interleukins - genetics; Interleukins - metabolism; Lipopolysaccharides - pharmacology; Liver - drug effects; Liver - immunology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Mice; Mice, Mutant Strains; Other diseases. Semiology; Receptor, Interferon alpha-beta - genetics; Receptors, Interleukin - genetics; Receptors, Interleukin - metabolism; RNA, Messenger - analysis; RNA, Messenger - metabolism; Spleen - drug effects; Spleen - immunology; STAT3 Transcription Factor - metabolism; Transcription, Genetic; Up-Regulation; IFNαβ receptor; APR; IL-24; IL-20 receptor 1; MyD88; signal transducer and activator of transcription; IL-22; LPS; IL-20; IFN; IL-22BP; Janus kinase; TLR; myeloid differentiation primary response gene product; Toll-like receptor; knockout; IL-20R2; IFNβ; KO; IFNAR; interferon; Endotoxin shock; IL-20R1; acute phase responses; STAT; interleukin-19; IL-19; JAK; IL-22 binding protein; Toll/IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β; lipopolysaccharide; TRIF; Shock; Liver; Endotoxin; Regulation(control); Reverse transcription polymerase chain reaction; Rodentia; Cytokine; Infection; Toxin; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Beta interferon; Bacteriosis; Interferon; Lesion; Molecular biology
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2006.08.009

Background/Aims The biological functions of the recently discovered IL-10-related cytokines IL-19, IL-20, IL-22, IL-24 and their receptors IL-20R1, IL-20R2 and IL-22R are not clear. Therefore, the expression of these cytokines and their receptors in the hepatic acute phase response to LPS was analysed. Type I interferons have important immunomodulatory functions in bacterial infections. We investigated if they influence release and organ-specific expression of TNF, IL-6 and IL-10 and the responsiveness of liver to IL-10 related cytokines during the reaction to LPS in vivo. Methods B6 and congenic IFNAR−/− mice were intraperitoneally injected with 5 mg/kg LPS. Systemic release of cytokines was quantified by ELISA. Organ-specific expression of cytokines and their receptors was evaluated by (semi quantitative or quantitative) RT-PCR. Results The cytokines IL-19, IL-22 and the IL-20R2 receptor subunit are up-regulated by LPS in the liver of normal mice. IFNα/β enhance the secretion and expression of IL-6 and IL-10 during the response to LPS, but also the up-regulation of IL-20R2 expression. Conclusions We show that the liver is a potential target for IL-19, IL-20 and IL-24. During an LPS response, IFNα/β influence cytokine secretion and expression and possibly the response to IL-19 and IL-24.