Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Investigation of the Immunomodulatory effect of Berberis vulgaris on core-pulsed dendritic cell vaccine

Authors: Doaa A. Ghareeb, Eiman H. Elwakeel, Rowaida Khalil, Mina S. Aziz, Maha A. El demellawy

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

Login to get access

Abstract

Background

Virus-induced dendritic cells (DCs) functional deficiency leads to sub-optimal initiation of adaptive immune responses and consequently chronic infection establishment. The present study reports an advanced hepatitis C virus (HCV) therapeutic vaccine model based on In vivo enrichment of DCs with barberry ethanolic crude extract (BCE) then pulsing them with HCV core protein.

Methods

DCs were enriched by BCE intravenous injection in BALB/c mice. Vaccine efficiency was assessed by flow cytometric analysis of splenocytes of immunized mice, cytokine profiling, cytotoxic T lymphocyte assay, and humoral immune response assessment.

Results

There was no significant difference in surface phenotypic characterization of splenocytes from mice immunized with non-BCE-enriched-core-pulsed DCs (iDcs-core) compared to those from mice injected with RPMI-1640 medium. However, splenocytes from mice immunized with BCE-enriched-core-pulsed DCs showed 197 % increase in CD16+ population, 33 % increase in MHCII+ population, and 43 % decrease in CD3+ population. In iDCs-core group, 57.9 % greater anti-core cytotoxic T lymphocyte activity, up-regulation in interferon gamma and interleukin (IL) -12 expression, and down-regulation in IL-4 and IL-10 were recorded. Moreover, sustained specific anti-core antibodies were detected only in sera of the same group.

Conclusions

results indicate that BCE-enriched-core-transduced DCs may serve as a new model for immunotherapy of HCV chronic infection.
Literature
1.
Ghany MG, Strader DB, Thomas DL, Seeff LB. American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335–74.CrossRefPubMed
2.
Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology (Baltimore, Md). 2013;57(4):1333–42.CrossRef
3.
Breban R, Doss W, Esmat G, Elsayed M, Hellard M, Ayscue P, Albert M, Fontanet A, Mohamed MK. Towards realistic estimates of HCV incidence in Egypt. J Viral Hepat. 2013;20(4):294–6.CrossRefPubMed
4.
Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M. The way forward in HCV treatment--finding the right path. Nat Rev Drug Discov. 2007;6(12):991–1000.CrossRefPubMed
5.
Coligan JE, Vogel S. Innate Immunity. In: Coligan JE, Bierer BE, Margulies DH, Shevach EM, Strober W, editors. Current Protocols in Immunology. Hoboken: Wiley; 2012. p. 1401–7.
6.
Landi A, Yu H, Babiuk LA, van Drunen Littel-van den Hurk S. Human dendritic cells expressing hepatitis C virus core protein display transcriptional and functional changes consistent with maturation. J Viral Hepat. 2011;18(10):700–13.CrossRefPubMed
7.
Wang JH, Layden TJ, Eckels DD. Modulation of the peripheral T-Cell response by CD4 mutants of hepatitis C virus: transition from a Th1 to a Th2 response. Hum Immunol. 2003;64(7):662–73.CrossRefPubMed
8.
9.
Foy E, Li K, Wang C, Sumpter Jr R, Ikeda M, Lemon SM, Gale Jr M. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science. 2003;300(5622):1145–8.CrossRefPubMed
10.
Ivanovska N, Philipov S. Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions, and pure alkaloids. Int Immunopharmacol. 1996;18:552–61.
11.
Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res. 2008;2(8):999–1012.CrossRef
12.
Kim T, kang B, Cho D, Kim S. Induction of interleukin-12 in mouse macrophage by berberine, a benzodioxoloquinolizine, deviates CD4+ T cells from Th2 to Th1 response. Immunology. 2003;109:407–14.CrossRefPubMedPubMedCentral
13.
Aziz M, Ghareeb D, Eweda S, Hussien H, El Demellawy M. Immunomodulatory effect of Berberis vulgaris extracts on murine splenocytes and enrichment of dendritic cells in vitro. Biotechnol Biotechnol Equip. 2015;29(6):1149–55.CrossRef
14.
Abd El-Wahab A, Ghareeb D, Sarhan E, Abu-Serie M, El Demellawy M. In vitro Biological and Therapeutic Effects of Berberis vulgaris and its Active Constituent, Berberine: Antioxidants, cholinergic, anti-diabetic and anticancer effects. BMC Complement. Altern Med. 2013;13:218.
15.
Ghareeb D, Abd El-Wahab AE, Sarhan EEM, Marwa M, Abu-Serie MM, El Demellawy MA. Biological assessment of Berberis vulgaris and its active constituent, berberine: Antibacterial, antifungal and anti-hepatitis C virus (HCV) effect. J Medicinal Plants Research. 2013;7(21):1529–36.
16.
National Health and Medical Research Council. Guidelines to promote the wellbeing of animals used for scientific purposes : the assessment and alleviation of pain and distress in research animals. 2008:1–189. doi:10.​1037/​e513122012-001.
17.
Sakai Y, Morrison BJ, Burke JD, Park JM, Terabe M, Janik JE, Forni G, Berzofsky JA, Morris JC. Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents. Cancer Res. 2004;64(21):8022–8.CrossRefPubMed
18.
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156–9.CrossRefPubMed
19.
Lazdina U, Hultgren C, Frelin L, Chen M, Lodin K, Weiland O, Leroux-Roels G, Quiroga JA, Peterson DL, Milich DR, Sällberg M. Humoral and CD4 (+) T helper (Th) cell responses to the hepatitis C virus non-structural 3 (NS3) protein: NS3 primes Th1-like responses more effectively as a DNA-based immunogen than as a recombinant protein. J Gen Virol. 2001;82(6):1299–308.CrossRefPubMed
20.
Nimmerjahn F, Ravetch JV. Fc gamma receptors as regulators of immune responses. Nat Rev Immunol. 2008;8(1):34–47.CrossRefPubMed
21.
de Baey A, Mende I, Riethmueller G, Baeuerle PA. Phenotype and function of human dendritic cells derived from M-DC8 (+) monocytes. Eur J Immunol. 2001;6:1646–55.CrossRef
22.
Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767–811.CrossRefPubMed
23.
Spear TT, Riley TP, Lyons GE, et al. Hepatitis C virus-cross-reactive TCR gene-modified T cells: a model for immunotherapy against diseases with genomic instability. J Leukoc Biol. 2016: doi:10.1189/jlb.2A1215-561R.
24.
Zhao L, Tyrrell DL. Myeloid dendritic cells can kill T cells during chronic hepatitis C virus infection. Viral Immunol. 2013;26(1):25–39.CrossRefPubMed
25.
Rosenberg S. Recent advances in the molecular biology of hepatitis C virus. J Mol Biol. 2001;313(3):451–64.CrossRefPubMed
26.
Kao CC, Yi G, Huang H. The core of hepatitis C virus pathogenesis. Curr Opin Virol. 2016;17:66–73.CrossRefPubMed
27.
28.
Saito K, Meyer K, Warner R, Basu A, Ray RB, Ray R. Hepatitis C Virus Core Protein Inhibits Tumor Necrosis Factor Alpha-Mediated Apoptosis by a Protective Effect Involving Cellular FLICE Inhibitory Protein. J Virol. 2006;80(9):4372–9.CrossRefPubMedPubMedCentral
29.
Hu X, Zimmerman MA, Bardhan K, Yang D, Waller JL, Liles GB, Lee JR, Pollock R, Lev D, Ware CF, Garber E, Bailly V, Browning JL, Liu K. Lymphotoxin β receptor mediates caspase-dependent tumor cell apoptosis in vitro and tumor suppression in vivo despite induction of NF-kB activation. Carcinogenesis. 2013;34(5):1105–14.CrossRefPubMedPubMedCentral
30.
Pavio N, Lai MM. The hepatitis C virus persistence: how to evade the immune system? J Biosci. 2003;28(3):287–304.CrossRefPubMed
31.
Larrubia JR, Moreno-Cubero E, Miquel J, Sanz-de-Villalobos E. Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control. World J Gastroenterol. 2015;21(12):3480–91.CrossRefPubMedPubMedCentral
32.
Valiante NM, D’Andrea A, Crotta S, Lechner F, Klenerman P, Nuti S, Wack A, Abrignani S. Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C. Immunol Rev. 2000;174:77–89.CrossRefPubMed
33.
Bain C, Fatmi A, Zoulim F, Zarski JP, Trépo C, Inchauspé G. Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology. 2001;120(2):512–4.CrossRefPubMed
34.
Auffermann-Gretzinger S, Keeffe EB, Levy S. Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood. 2001;97(10):3171–6.CrossRefPubMed
35.
Malta FM, Bruno FR, Carvalho KI, Nastri AC, Kalil J, Carrilho FJ, et al. HCV viremia drives an increment of CD86 expression by myeloid dendritic cells. J Med Virol. 2013;85(11):1919–24.CrossRefPubMed
36.
Zhu HH, Xu KL, Pan XY, Liu JQ, Chen FX, Huang YH. Specific anti-leukemic cell effect mediated by dendritic cells pulsed with chronic myelogenous leukemia lysate antigen in vitro. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2003;11(3):278–81.PubMed
37.
Berhanu A, Huang J, Alber SM, Watkins SC, Storkus WJ. Combinational FLt3 ligand and granulocyte macrophage colony-stimulating factor treatment promotes enhanced tumor infiltration by dendritic cells and antitumor CD8 (+) T-cell cross-priming but is ineffective as a therapy. Cancer Res. 2006;66(9):4895–903.CrossRefPubMed
38.
Randolph GJ, Sanchez-Schmitz G, Liebman RM, Schäkel k. The CD16+ (FcγRIII+) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting. J Exp Med. 2002;196(4):517–27.CrossRefPubMedPubMedCentral
39.
Mende I, Hoffmann P, Wolf A, Lutterbüse R, Kopp E, Baeuerle PA, de Baey A, Kufer P. Highly efficient antigen targeting to M-DC8+ dendritic cells via FcgammaRIII/CD16-specific antibody conjugates. Int Immunol. 2005;17(5):539–47.CrossRefPubMed
40.
Haverson K, Singha S, Stokes CR, Bailey M. Professional and non-professional antigen-presenting cells in the porcine small intestine. Immunology. 2000;101(4):492–500.CrossRefPubMedPubMedCentral
41.
Liu H, Rhodes M, Wiest DL, Vignali DA. On the dynamics of TCR:CD3 complex cell surface expression and down modulation. Immunity. 2000;13(5):665–75.CrossRefPubMed
42.
Dolganiuc A, Chang S, Kodys K, Mandrekar P, Bakis G, Cormier M, Szabo G. Hepatitis C virus (HCV) core protein-induced, monocyte-mediated mechanisms of reduced IFN-alpha and plasmacytoid dendritic cell loss in chronic HCV infection. J Immunol. 2006;177(10):6758–68.CrossRefPubMed
43.
Stone AEL, Mitchell A, Brownell J, et al. Hepatitis C virus core protein inhibits interferon production by a human plasmacytoid dendritic cell line and dysregulates interferon regulatory factor-7 and signal transducer and activator of transcription (STAT) 1 protein expression. PLoS One. 2014;9(5):e95627.CrossRefPubMedPubMedCentral
44.
Bacchetta R, Gregori S, Roncarolo MG. CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun Rev. 2005;4(8):491–6.CrossRefPubMed
45.
Yamane H, Paul WE. Early signaling events that underlie fate decisions of naive CD4 (+) T cells toward distinct T-helper cell subsets. Immunol Rev. 2013;252(1):12–23.CrossRefPubMedPubMedCentral
46.
MacQuillan GC, Mamotte C, Reed WD, Jeffrey GP, Allan JE. Upregulation of endogenous intrahepatic interferon stimulated genes during chronic hepatitis C virus infection. J Med Virol. 2003;70(2):219–27.CrossRefPubMed
47.
48.
Schurich A, Pallett LJ, Lubowiecki M, et al. The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells. PLoS Pathog. 2013;9(3):e1003208.CrossRefPubMedPubMedCentral
49.
Spanakis NE, Garinis GA, Alexopoulos EC, et al. Cytokine serum levels in patients with chronic HCV infection. J Clin Lab Anal. 2002;16(1):40–6.CrossRefPubMed
50.
Reiser M, Marousis CG, Nelson DR, Lauer G, González-Peralta RP, Davis GL, Lau JY. Serum interleukin 4 and interleukin 10 levels in patients with chronic hepatitis C virus infection. J Hepatol. 1997;26(3):471–8.CrossRefPubMed
51.
Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10(3):170–81.CrossRefPubMed
52.
53.
Gigi E, Raptopoulou-Gigi M, Kalogeridis A, Masiou S, Orphanou E, Vrettou E, Lalla TH, Sinakos E, Tsapas V. Cytokine mRNA expression in hepatitis C virus infection: TH1 predominance in patients with chronic hepatitis C and TH1-TH2 cytokine profile in subjects with self-limited disease. J Viral Hepat. 2008;2:145–54.
54.
Jiang C, Magee DM, Cox RA. Construction of a single-chain interleukin-12-expressing retroviral vector and its application in cytokine gene therapy against experimental coccidioidomycosis. Infect Immun. 1999;67(6):2996–3001.PubMedPubMedCentral
55.
56.
Roozendaal R, Vellenga E, Postma DS, De Monchy JGR, Kauffman HF. Nitric oxide selectively decreases interferonγ expression by activated human T lymphocytes via a cGMP‐independent mechanism. Immunol. 1999;98(3):393–9.CrossRef
Metadata
Title
Investigation of the Immunomodulatory effect of Berberis vulgaris on core-pulsed dendritic cell vaccine
Authors
Doaa A. Ghareeb
Eiman H. Elwakeel
Rowaida Khalil
Mina S. Aziz
Maha A. El demellawy
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1327-2

Other articles of this Issue 1/2016

BMC Complementary Medicine and Therapies 1/2016 Go to the issue

Research article

Rutin attenuates intestinal toxicity induced by Methotrexate linked with anti-oxidative and anti-inflammatory effects

Research article

Haloalkane induced hepatic insult in murine model: amelioration by Oleander through antioxidant and anti-inflammatory activities, an in vitro and in vivo study

Research article

Protective effect of fermented Cyclopia intermedia against UVB-induced damage in HaCaT human keratinocytes

Research article

Studies on the therapeutic effect of propolis along with standard antibacterial drug in Salmonella enterica serovar Typhimurium infected BALB/c mice

Research article

Ancient peat and apple extracts supplementation may improve strength and power adaptations in resistance trained men

Research article

Evaluation of Hepatoprotective activity of Eriocaulon quinquangulare in vitro using porcine liver slices against ethanol induced liver toxicity and free radical scavenging capacity