1. bookVolume 21 (2013): Issue 1 (March 2013)
Journal Details
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eISSN
2284-5623
ISSN
2284-5623
First Published
08 Aug 2013
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4 times per year
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English
access type Open Access

The serum level of the immunomodulatory peptide cathelicidin LL37 and T helper cell type 1 inflammatory response in viral hepatitis B, C, and D

Journal Details
License
Format
Journal
eISSN
2284-5623
ISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

Cathelicidin LL37 is an innate immunity antimicrobial peptide involved in the immune modulation of IFN-Abstract Cathelicidin LL37 is an innate immunity antimicrobial peptide involved in the immune modulation of IFN-γ, the key cytokine of T helper cell type 1 (Th1) response. The role of LL37 in viral hepatitis inflammation is unknown. We assessed the serum variations of LL37 and the Th1 response in hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis D virus (HDV) infections. The LL37 level (Elisa detection) and Th1 response (defined by IFN-γ level, CD4+ and CD8+ T cell count) were analyzed in 87 patients: 65 hepatitis patients (34 HCV, 18 HBV, 13 HDV) and 22 healthy controls. The subjects, 33 males/ 54 women aged 20-64 years, were selected at "Matei Bals" Institut, Bucharest, Romania. Hepatitis patients were classified according to viral etiology and viral replication as active cases (detectable viremia) versus negative cases (undetectable viremia). Student T test and Mann Whitney analysis were applied. High levels of LL37 (138.09±88.45ng/ml, p=0.045) and IFN-γ (69.82 pg/ml, p=0.005) were detected in the whole group of hepatitis. Active HCV hepatitis presented a significant increase in LL37 level (155.15±78.84ng/ml, p=0.014) and Th1 response by comparison with inactive HCV hepatitis. Conversely active HBV patients displayed low LL37 levels (76.75ng/ml, p=0.009) and no Th1 dominant response by comparison with inactive B hepatitis. High levels of LL37 up to 171.01±72.08 ng/ml and a moderate Th1 response defined HDV patients. Our results highlights increased levels of the cathelicidin LL37 in all viral hepatitis correlated with a strong and concordant immune response in active HCV hepatitis. , the key cytokine of T helper cell type 1 (Th1) response. The role of LL37 in viral hepatitis inflammation is unknown. We assessed the serum variations of LL37 and the Th1 response in hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis D virus (HDV) infections. The LL37 level (Elisa detection) and Th1 response (defined by IFN-γ level, CD4+ and CD8+ T cell count) were analyzed in 87 patients: 65 hepatitis patients (34 HCV, 18 HBV, 13 HDV) and 22 healthy controls. The subjects, 33 males/ 54 women aged 20-64 years, were selected at "Matei Bals" Institut, Bucharest, Romania. Hepatitis patients were classified according to viral etiology and viral replication as active cases (detectable viremia) versus negative cases (undetectable viremia). Student T test and Mann Whitney analysis were applied. High levels of LL37 (138.09±88.45ng/ml, p=0.045) and IFN-γ (69.82 pg/ml, p=0.005) were detected in the whole group of hepatitis. Active HCV hepatitis presented a significant increase in LL37 level (155.15±78.84ng/ml, p=0.014) and Th1 response by comparison with inactive HCV hepatitis. Conversely active HBV patients displayed low LL37 levels (76.75ng/ml, p=0.009) and no Th1 dominant response by comparison with inactive B hepatitis. High levels of LL37 up to 171.01±72.08 ng/ml and a moderate Th1 response defined HDV patients. Our results highlights increased levels of the cathelicidin LL37 in all viral hepatitis correlated with a strong and concordant immune response in active HCV hepatitis.

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1. Zanetti M, Gennaro R, Romeo D. Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett. 1995; 374: 1-5.10.1016/0014-5793(95)01050-OSearch in Google Scholar

2. Nizet V, Gallo RL. Cathelicidins and innate defense against invasive bacterial infection. Scand J Infect Dis 2003; 35: 670-676.10.1080/0036554031001562914620153Search in Google Scholar

3. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 2002; 169:3883-3891.10.4049/jimmunol.169.7.388312244186Search in Google Scholar

4. Nijnik A, Pistolic J, Wyatt A, Tam S, Hancock R. Human Cathelicidin Peptide LL-37 Modulates the Effects of IFN-γ on APCs. The Journal of Immunology 2009; 183 (9) 5788-5798.10.4049/jimmunol.090149119812202Search in Google Scholar

5. Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, The human antimicrobial and chemotactic peptides LL-37 are expressed by specific lymphocyte and monocyte populations. Blood 2000; 96 (9): 3086-3093.10.1182/blood.V96.9.3086Search in Google Scholar

6. Davidson DJ. The cationic antimicrobial peptide LL37 modulates dendritic cell differentiation. J Immunol 2004; 172(2):1146-1156.10.4049/jimmunol.172.2.114614707090Search in Google Scholar

7. Bucki R, Leszczynska K, Namiot A, Sokolowski W.Cathelicidin LL37: a multitask antimicrobial peptide. Arch Immunol Ther Exp 2010; 58:15-25.10.1007/s00005-009-0057-220049649Search in Google Scholar

8. Kandler K, Shaykhiev R, Kleemann P,Klesca F, Lohoff M, Vogelmeier . C The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands, Int. Immunol. (2006) 18 (12): 1729-173610.1093/intimm/dxl10717041145Search in Google Scholar

9. Mookherjee N, Brown KL, Bowdish D, Doria S, Falsafi R, Hokamp K et al. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. The Journal of Immunology 2006; 176: 2455-2464.10.4049/jimmunol.176.4.245516456005Search in Google Scholar

10. Doss M, White M, Tecle T, Hartshorn KL, Human defensins and LL-37 in mucosal immunity, Journal of Leukocyte Biology 2010; 87 (1);79-9210.1189/jlb.0609382716708619808939Search in Google Scholar

11. Golec M. Cathelicidin LL-37: LPS-neutralizing, pleiotropic peptide. Ann Agric Environ Med 2007; 14(1):1-4.Search in Google Scholar

12. Rivas-Santiago B, Hernandez-Pando R, Carranza C. Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells. Infection and Immunity 2008; 76 (3): 935-94110.1128/IAI.01218-07225880118160480Search in Google Scholar

13. Cole AM, Lehrer RI. Minidefensins and other antimicrobial peptides: candidate anti-HIV microbicides. Expert Opin Ther Targets 2003; 7:329-341. doi: 10.1517/eott.7.3.329.2243610.1517/eott.7.3.329.22436Search in Google Scholar

14. Andersson E, Rydengård V, Sonesson A, Mörgelin M, Björck L, Schmidtchen A. Antimicrobial activities of heparin-binding peptides, 2004, European Journal of Biochemistry 271 (6);1219-122610.1111/j.1432-1033.2004.04035.x15009200Search in Google Scholar

15. Taylor JM, Han Z. Purinergic Receptor Functionality Is Necessary for Infection of Human Hepatocytes by Hepatitis Delta Virus and Hepatitis B Virus, PLoS One. 2010; 5(12): e15784.doi: 10.1371/journal.pone.001578410.1371/journal.pone.0015784300496121187936Search in Google Scholar

16. Barth H, Schnober EK, Zhang F, Linhardt RJ, Depla E, Boson B et al. Viral and cellular determinants of the hepatitis C virus envelope-heparan sulfate interaction. Journal of Virology 2006; 80 (21): 10579-10590.10.1128/JVI.00941-06164178316928753Search in Google Scholar

17. Kaneider NK, Djanani A, Wiedermann CJ. Heparan sulfate proteoglycan-involving immunomodulation by cathelicidin antimicrobial peptides and PR39”. The Scientific World Journal 2007; 7:1832-1838.10.1100/tsw.2007.285590085018040544Search in Google Scholar

18. Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 1999; 96(22):12766-12771.10.1073/pnas.96.22.127662309010535997Search in Google Scholar

19. Sørensen O, Bratt T, Anders H, Madsen MT, Borregaard N. The human antibacterial cathelicidin, hCAP-18, is bound to lipoproteins in plasma, The Journal of Biological Chemistry 1999; 274(32): 22445-22451Search in Google Scholar

20. Guidelines For Viral Hepatitis Surveillance And Case Management, 2009 http://www.cdc.gov/hepatitis/SurveillanceGuidelines.htm).Search in Google Scholar

21. Laborator Synevo.Ghidul serviciilor medicale. Referinte specifice tehnologiei de lucru utilizate editia. Catalog 2007-2008: 555-562 http://www.synevo.com.roSearch in Google Scholar

22. Nascimbeni M, Mizukoshi E, Bosmann M, Major ME, Mihalik K, Rice CM et al. Kinetics of CD4+ and CD8+ memory T-cell responses during hepatitis C virus rechallenge of previously recovered chimpanzees. Journal of Virology 2003; 77 (8): 4781-4793.10.1128/JVI.77.8.4781-4793.200315213112663785Search in Google Scholar

23. Eckels DD, Wang H, Bian TH, Tabatabai N, Gill JC. Immunobiology of hepatitis C virus (HCV) infection: the role of CD4 T cells in HCV infection. Immunol Rev 2000; 174: 90-97.10.1034/j.1600-0528.2002.017403.x10807509Search in Google Scholar

24. Yang PL, Althage A, Chung J, Maier H, Wieland S, Isogawa M et al. Immune effectors required for hepatitis B virus clearance. PNAS 2010; 107 (2): 798-802.10.1073/pnas.0913498107281893320080755Search in Google Scholar

25. Napoli J, Bishop GA, McGuinness PH, Painter DM, McCaughan GW. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines. Hepatology 1996; 24: 759-765.10.1002/hep.510240402Search in Google Scholar

26. Frese M, Schwarzle V, Barth K et al. Interferon- gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology 2002; 35: 694-70310.1053/jhep.2002.31770Search in Google Scholar

27. Kondo Y, Sung VM, Machida K, Liu M, Lai MM. Hepatitis C virus infects T cells and affects interferon- gamma signaling in T cell lines. Virology 2007; 361(1): 161-173.10.1016/j.virol.2006.11.009Search in Google Scholar

28. Tjabringa GS, Rabe K, Hiemstra P. The human cathelicidin LL-37: a multifunctional peptide involved in infection and inflammation in the lung Pulmonary Pharmacology & Therapeutics 2009; 18 (5); 321-327.10.1016/j.pupt.2005.01.001Search in Google Scholar

29. Sørensen, O, Cowland JB, Askaa J, Borregaard N. An ELISA for hCAP-18, the cathelicidin present in human neutrophils and plasma. J. Immunol Methods 1997; 206: 53-59.10.1016/S0022-1759(97)00084-7Search in Google Scholar

30. Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA Jr, Koeffler HP et al. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis 2009; 48(4):418-424.10.1086/596314694431119133797Search in Google Scholar

31. Yamschchikov AV, Kurbatova EV, Kumari M, Blumberg HM, Ziegler TR, Ray SM et al. Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis. Am J Clin Nutr September 2010; 92 (3) 603-611.10.3945/ajcn.2010.29411292153720610636Search in Google Scholar

32. Iacob SA, Panaitescu E, Iacob DG, Cojocaru M. The human cathelicidin LL37 peptide has high plasma levels in B and C hepatitis related to viral activity but not to 25-hydroxyvitamin D plasma level. Rom J Intern Med 2012;50(3):217-23. Search in Google Scholar

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