Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/305492
Title:
Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells.
Authors:
Saeed, A; Baloch, K; Brown, R J P; Wallis, R; Chen, L; Dexter, L; McClure, C P; Shakesheff, K; Thomson, B J
Abstract:
Mannan binding lectin (MBL)-associated serine protease type 1 (MASP-1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP-1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus (HCV) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP-1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells (HSCs) and may additionally be up-regulated by HCV. In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP-1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up-regulation of HSC activation markers α-smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP-1 was up-regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP-1 and provide a possible mechanistic link between high levels of MASP-1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP-1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease.
Affiliation:
School of Molecular Medical Sciences, University of Nottingham, Leicester, UK; School of Pharmacy, University of Nottingham, Leicester, UK.
Citation:
Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells. 2013, 174 (2):265-73 Clin. Exp. Immunol.
Journal:
Clinical and experimental immunology
Issue Date:
Nov-2013
URI:
http://hdl.handle.net/10033/305492
DOI:
10.1111/cei.12174
PubMed ID:
23841802
Type:
Article
Language:
en
ISSN:
1365-2249
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorSaeed, Aen
dc.contributor.authorBaloch, Ken
dc.contributor.authorBrown, R J Pen
dc.contributor.authorWallis, Ren
dc.contributor.authorChen, Len
dc.contributor.authorDexter, Len
dc.contributor.authorMcClure, C Pen
dc.contributor.authorShakesheff, Ken
dc.contributor.authorThomson, B Jen
dc.date.accessioned2013-11-18T14:13:32Z-
dc.date.available2013-11-18T14:13:32Z-
dc.date.issued2013-11-
dc.identifier.citationMannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells. 2013, 174 (2):265-73 Clin. Exp. Immunol.en
dc.identifier.issn1365-2249-
dc.identifier.pmid23841802-
dc.identifier.doi10.1111/cei.12174-
dc.identifier.urihttp://hdl.handle.net/10033/305492-
dc.description.abstractMannan binding lectin (MBL)-associated serine protease type 1 (MASP-1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP-1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus (HCV) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP-1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells (HSCs) and may additionally be up-regulated by HCV. In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP-1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up-regulation of HSC activation markers α-smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP-1 was up-regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP-1 and provide a possible mechanistic link between high levels of MASP-1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP-1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease.en
dc.language.isoenen
dc.rightsArchived with thanks to Clinical and experimental immunologyen
dc.titleMannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells.en
dc.typeArticleen
dc.contributor.departmentSchool of Molecular Medical Sciences, University of Nottingham, Leicester, UK; School of Pharmacy, University of Nottingham, Leicester, UK.en
dc.identifier.journalClinical and experimental immunologyen

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