Expression and upregulation of cathepsin S and other early molecules required for antigen presentation in activated hepatic stellate cells upon IFN-gamma treatment.
Hepatic stellate cells (HSCs) have been shown to be able to activate T-cells and upregulate expression of surface molecules essential for this process, when treated with IFN-gamma. But little is known about the early molecules expressed by activated hepatic stellate cells under the same treatment. In this study, we investigate the effect of IFN-gamma on the transcription and expression of these early molecules in hepatic stellate cells. We show on the molecular level that activated rat hepatic stellate cells express the class II transactivator, the invariant chain (CD74), the MHC class II molecules, as well as cathepsin S, all of which are known to be responsible for the initial steps of successful antigen presentation. The mRNA and the protein expression level of these molecules is upregulated by IFN-gamma. Importantly, IFN-gamma increases cathepsin S activity, suggesting a possible involvement of this protease in CD74 processing. Our data also show that not only can the HSCs take up antigenic proteins, they can also process them. Our comparative study indicates that the rat HSC-T6 cell line displays sufficient similarity to the activated rat HSCs in order to serve as a model for in vitro studies on the molecular mechanisms of inflammatory response.
Maubach
Gunter
G
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore. gmaubach@ibn.a-star.edu.sg
Lim
Michelle Chin Chia
MC
Kumar
Saravana
S
Zhuo
Lang
L
D000418:Albumins / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics* / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D005453:Fluorescence; D006681:HLA-D Antigens / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
D000418:Albumins; D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C045084:invariant chain; D007371:Interferon-gamma; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534280:Ctsl protein, rat; C028217:cathepsin S