PMID- 19804500 OWN - NLM STAT- MEDLINE DCOM- 20101101 LR - 20211020 IS - 1365-2893 (Electronic) IS - 1352-0504 (Print) IS - 1352-0504 (Linking) VI - 17 IP - 8 DP - 2010 Aug TI - Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells. PG - 555-62 LID - 10.1111/j.1365-2893.2009.01213.x [doi] AB - Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Immature DCs (iDCs) were established from healthy donor peripheral blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4. Lipopolysaccharide was used to establish mature DCs (mDCs). Cells were then pulsed with HCV recombinant proteins or transfected with HCV plasmids and subsequently assayed for cell surface marker expression by flow cytometry. For cytokine and proliferative T-cell response analysis, DCs were cultured with autologous CD4 T cells and tuberculin purified protein derivative (PPD). Mean fluorescent intensity of CD86 was reduced in HCV protein-pulsed iDCs. Proliferative T-cell responses and Th1 cytokine concentrations were reduced with HCV nonstructural proteins (NS), particularly with HCV NS4. HCV nonstructural proteins, particularly NS4, change the iDC phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions. FAU - Takaki, A AU - Takaki A AD - Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. akitaka@md.okayama-u.ac.jp FAU - Tatsukawa, M AU - Tatsukawa M FAU - Iwasaki, Y AU - Iwasaki Y FAU - Koike, K AU - Koike K FAU - Noguchi, Y AU - Noguchi Y FAU - Shiraha, H AU - Shiraha H FAU - Sakaguchi, K AU - Sakaguchi K FAU - Nakayama, E AU - Nakayama E FAU - Yamamoto, K AU - Yamamoto K LA - eng PT - Journal Article DEP - 20091004 PL - England TA - J Viral Hepat JT - Journal of viral hepatitis JID - 9435672 RN - 0 (Cytokines) RN - 0 (NS4 protein, hepatitis C virus) RN - 0 (Recombinant Proteins) RN - 0 (Viral Nonstructural Proteins) SB - IM MH - Adult MH - Cell Polarity/immunology MH - Cytokines/immunology MH - Dendritic Cells/cytology/*immunology MH - Flow Cytometry MH - Hepacivirus/*immunology MH - Hepatitis C, Chronic/*immunology/virology MH - Humans MH - Lymphocyte Activation/immunology MH - Male MH - Plasmids/immunology MH - Recombinant Proteins/*immunology MH - Statistics, Nonparametric MH - Th1 Cells/*immunology MH - Viral Nonstructural Proteins/*immunology PMC - PMC2916225 EDAT- 2009/10/07 06:00 MHDA- 2010/11/03 06:00 CRDT- 2009/10/07 06:00 PHST- 2009/10/07 06:00 [entrez] PHST- 2009/10/07 06:00 [pubmed] PHST- 2010/11/03 06:00 [medline] AID - JVH1213 [pii] AID - 10.1111/j.1365-2893.2009.01213.x [doi] PST - ppublish SO - J Viral Hepat. 2010 Aug;17(8):555-62. doi: 10.1111/j.1365-2893.2009.01213.x. Epub 2009 Oct 4.