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.
OBJECTIVE
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 5mg/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. IFNalpha/beta 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, IFNalpha/beta influence cytokine secretion and expression and possibly the response to IL-19 and IL-24.
Wegenka
Ursula Maria
UM
Department of Internal Medicine I, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany. ursula.wegenka@uniklinik-ulm.de
Dikopoulos
Nektarios
N
Reimann
Jörg
J
Adler
Guido
G
Wahl
Christian
C
D000209:Acute-Phase Proteins / Q000032:analysis; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014158:Transcription, Genetic; D015854:Up-Regulation; D000099180:Interleukin-24
D000209:Acute-Phase Proteins; D016207:Cytokines; D007370:Interferon Type I; D016753:Interleukin-10; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000099180:Interleukin-24; C498891:Il19 protein, mouse; C494087:Stat3 protein, mouse; C492510:interleukin-20 receptor; C422042:interleukin 20