Abstract
Aim:
The aim of the present study was to investigate the expression of Toll-like receptors (TLR) 7 and 9 in peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B virus (HBV) infection and related hepatocellular carcinoma.
Methods:
The study group was comprised of 52 patients: 41 with chronic hepatitis B and 11 healthy controls. The protein and mRNA levels of TLR7 and TLR9 were evaluated using real-time PCR, Western blot analysis, and flow cytometry. We also detected the serum viral load of HBV in the patients and analyzed the correlation between HBV-DNA copies and the TLR expression.
Results:
Our results demonstrated a lower TLR7 expression in all HBV infection groups compared to the controls. We found that HBV infection led to a decreased expression of TLR9 mRNA, but an increased expression of the TLR9 protein compared to the healthy group. The TLR protein levels are related to serum HBV-DNA (P<0.01).
Conclusion:
There are downregulations of TLR7 expression and TLR9 mRNA in PBMC of HBV-infected patients, but an increased TLR9 expression at the protein level.
Similar content being viewed by others
Article PDF
References
Visvanathan K, Lewin SR . Immunopathogenesis: role of innate and adaptive immune responses. Semin Liver Dis 2006; 26: 104–15.
Chisari FV, Ferrari C . Hepatitis B virus immunopathogenesis. Annu Rev Immunol 1995; 13: 29–60.
Medzhitov R, Janeway C Jr Innate immune recognition: mechanisms and pathways. Immunol Rev 2000; 173: 89–97.
Werling D, Jungi TW . TOLL-like receptors linking innate and adaptive immune response. Vet Immunol Immunopathol 2003; 91: 1–12.
Takeda K, Akira S . Toll-like receptors in innate immunity. Int Immunol 2005; 17: 1–14.
Janeway CA Jr, Medzhitov R . Innate immune recognition. Annu Rev Immunol 2002; 20: 197–216.
Iwasaki A, Medzhitov R . Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004; 5: 987–95.
Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T, et al. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 2002; 168: 4531–7.
Takeda K, Kaisho T, Akira S . Toll-like receptors. Annu Rev Immunol 2003; 21: 335–76.
Andersen JM, Al-Khairy D, Ingalls RR . Innate immunity at the mucosal surface: role of toll-like receptor 3 and toll-like receptor 9 in cervical epithelial cell responses to microbial pathogens. Biol Reprod 2006; 74: 824–31.
Droemann D, Albrecht D, Gerdes J, Ulmer AJ, Branscheid D, Vollmer E, et al. Human lung cancer cells express functionally active Toll-like receptor 9. Respir Res 2005; 6: 1.
Merrell MA, Ilvesaro JM, Lehtonen N, Sorsa T, Gehrs B, Rosenthal E, et al. Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res 2006; 4: 437–47.
Schlaepfer E, Audige A, Joller H, Speck RF . TLR7/8 triggering exerts opposing effects in acute versus latent HIV infection. J Immunol 2006; 176: 2888–95.
Ito T, Wang YH, Liu YJ . Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Tolllike receptor (TLR) 7 and TLR9. Springer Semin Immunopathol 2005; 26: 221–9.
Yang K, Puel A, Zhang S, Eidenschenk C, Ku CL, Casrouge A, et al. Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda is IRAK-4 dependent and redundant for protective immunity to viruses. Immunity 2005; 23: 465–78.
Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M . Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 2004; 103: 1433–7.
Huang YH, Chou MH, Du YY, Huang CC, Wu CL, Chen CL, et al. Expression of toll-like receptors and type 1 interferon specific protein MxA in biliary atresia. Lab Invest 2006; 87: 66–74.
Lesmeister MJ, Bothwell MR, Misfeldt ML . Toll-like receptor expression in the human nasopharyngeal tonsil (adenoid) and palantine tonsils: a preliminary report. Int J Pediatr Otorhinolaryngol 2006; 70: 987–92.
Chinese Society of Hepatology and Chinese Society of Infectious Diseases CMA. The guideline of prevention and treatment for chronic hepatitis B. Chin J Hepatol 2005; 13: 881–90.
Ross JW, Ashworth MD, Hurst AG, Malayer JR, Geisert RD . Analysis and characterization of differential gene expression during rapid trophoblastic elongation in the pig using suppression subtractive hybridization. Reprod Biol Endocrinol 2003; 1: 23.
Chuang TH, Ulevitch RJ . Cloning and characterization of a subfamily of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur Cytokine Netw 2000; 11: 372–8.
Du X, Poltorak A, Wei Y, Beutler B . Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 2000; 11: 362–71.
Isogawa M, Robek MD, Furuichi Y, Chisari FV . Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol 2005; 79: 7269–72.
An H, Xu H, Yu Y, Zhang M, Qi R, Yan X, et al. Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways. Immunol Lett 2002; 81: 165–9.
McKimmie CS, Johnson N, Fooks AR, Fazakerley JK . Viruses selectively upregulate Toll-like receptors in the central nervous system. Biochem Biophys Res Commun 2005; 336: 925–33.
McBride S, Walsh D, Meleady P, Daly N, Clynes M . Bromodeoxyuridine induces keratin protein synthesis at a posttranscriptional level in human lung tumour cell lines. Differentiation 1999; 64: 185–93.
Gygi SP, Rochon Y, Franza BR, Aebersold R . Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 1999; 19: 1720–30.
Anderson L, Seilhamer J . A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 1997; 18: 533–7.
Chen G, Gharib TG, Huang CC, Taylor JM, Misek DE, Kardia SL, et al. Discordant protein and mRNA expression in lung adenocarcinomas. Mol Cell Proteomics 2002; 1: 304–13.
Leifer CA, Kennedy MN, Mazzoni A, Lee C, Kruhlak MJ, Segal DM . TLR9 is localized in the endoplasmic reticulum prior to stimulation. J Immunol 2004; 173: 1179–83.
Bauer S . Toll-erating self DNA. Nat Immunol 2006; 7: 13–5.
Barton GM, Kagan JC, Medzhitov R . Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol 2006; 7: 49–56.
Schmausser B, Andrulis M, Endrich S, Lee SK, Josenhans C, Muller-Hermelink HK, et al. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin Exp Immunol 2004; 136: 521–6.
Lee J, Rachmilewitz D, Raz E . Homeostatic effects of TLR9 signaling in experimental colitis. Ann N Y Acad Sci 2006; 1072: 351–5.
Eaton-Bassiri A, Dillon SB, Cunningham M, Rycyzyn MA, Mills J, Sarisky RT, et al. Toll-like receptor 9 can be expressed at the cell surface of distinct populations of tonsils and human peripheral blood mononuclear cells. Infect Immun 2004; 72: 7202–11.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Xu, N., Yao, Hp., Sun, Z. et al. Toll-like receptor 7 and 9 expression in peripheral blood mononuclear cells from patients with chronic hepatitis B and related hepatocellular carcinoma. Acta Pharmacol Sin 29, 239–244 (2008). https://doi.org/10.1111/j.1745-7254.2008.00711.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2008.00711.x
Keywords
This article is cited by
-
TLR9 gene polymorphism −1486T/C (rs187084) is associated with uterine cervical neoplasm in Mexican female population
Journal of Cancer Research and Clinical Oncology (2017)
-
The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility
BMC Cancer (2012)
-
Constructing the HBV-human protein interaction network to understand the relationship between HBV and hepatocellular carcinoma
Journal of Experimental & Clinical Cancer Research (2010)
-
The Incidence and Significance of Pattern-Recognition Receptors in Chronic Viral Hepatitis Types B and C in Man
Archivum Immunologiae et Therapiae Experimentalis (2010)