TY - JOUR
T1 - Impaired interferon type I signalling in the liver modulates the hepatic acute phase response in hepatitis C virus transgenic mice
AU - Wegert, Mona
AU - Monica, Nicola La
AU - Tripodi, Marco
AU - Adler, Guido
AU - Dikopoulos, Nektarios
PY - 2009/8
Y1 - 2009/8
N2 - Background/Aims: The immunomodulatory active hepatitis C virus (HCV) has been shown to interfere with antiviral interferon (IFN) type I functions. The aim of the study was to determine whether further basic innate immunologic functions are influenced by HCV. Methods: The acute phase response (APR) was induced in HCV transgenic (tg) mice and C57BL/6J control mice using lipopolysaccharide. Activation of transcription factors, mRNA expression and production of cytokines and acute phase proteins (APP) were determined. IFN type I and tumor necrosis factor (TNF) α signalling were investigated after polyI:C or TNF-α treatment. Results: HCV tg mice showed an attenuated APR: hepatic activation of nuclear factor κ B (NFκB) and interferon-stimulated gene factor 3 (ISGF3), hepatic expression of interleukin (IL) 6, IL-10, and IFN-γ mRNA, serum concentrations of IL-6 and IFN-γ and production of type II acute phase proteins were reduced compared to wild-type mice. While no differences in NFκB activation could be detected after TNF-α injection, HCV tg mice showed reduced activation of ISGF3 and reduced transactivation of IFN target genes after polyI:C treatment. Conclusions: Besides antiviral defence mechanisms, interruption of IFN type I signalling by HCV modulates the APR which is aimed at a variety of pathogens.
AB - Background/Aims: The immunomodulatory active hepatitis C virus (HCV) has been shown to interfere with antiviral interferon (IFN) type I functions. The aim of the study was to determine whether further basic innate immunologic functions are influenced by HCV. Methods: The acute phase response (APR) was induced in HCV transgenic (tg) mice and C57BL/6J control mice using lipopolysaccharide. Activation of transcription factors, mRNA expression and production of cytokines and acute phase proteins (APP) were determined. IFN type I and tumor necrosis factor (TNF) α signalling were investigated after polyI:C or TNF-α treatment. Results: HCV tg mice showed an attenuated APR: hepatic activation of nuclear factor κ B (NFκB) and interferon-stimulated gene factor 3 (ISGF3), hepatic expression of interleukin (IL) 6, IL-10, and IFN-γ mRNA, serum concentrations of IL-6 and IFN-γ and production of type II acute phase proteins were reduced compared to wild-type mice. While no differences in NFκB activation could be detected after TNF-α injection, HCV tg mice showed reduced activation of ISGF3 and reduced transactivation of IFN target genes after polyI:C treatment. Conclusions: Besides antiviral defence mechanisms, interruption of IFN type I signalling by HCV modulates the APR which is aimed at a variety of pathogens.
KW - Acute phase proteins
KW - Chronic infection
KW - Interferon gamma
KW - Interferon resistance
KW - Interferon target genes
KW - Interferon-stimulated gene factor 3
KW - Interleukin 10
KW - Interleukin 6
KW - Lipopolysaccharide
UR - http://www.scopus.com/inward/record.url?scp=67649227091&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649227091&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2009.03.014
DO - 10.1016/j.jhep.2009.03.014
M3 - Article
C2 - 19464068
AN - SCOPUS:67649227091
VL - 51
SP - 271
EP - 278
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -