nach oben

Erschienen in:

01.04.2011 | Original Article

HCV-Related Proteins Activate Kupffer Cells Isolated from Human Liver Tissues

verfasst von: Naohiro Hosomura, Hiroshi Kono, Masato Tsuchiya, Kenichi Ishii, Masahito Ogiku, Masanori Matsuda, Hideki Fujii

Erschienen in: Digestive Diseases and Sciences | Ausgabe 4/2011

Einloggen, um Zugang zu erhalten

Abstract

Purpose

It was reported from this laboratory that Kupffer cells (KCs) were activated in patients infected with HCV. Since dendritic cells, monocytes, and macrophages were activated by stimulation with HCV-related proteins, the specific aim of this study was to investigate the role of HCV-related proteins in activation of KCs, the signal pathway of activation of KCs mediated by Toll-like receptor (TLR) 4, and the influence of HCV infection on function of KCs.

Methods

Kupffer cells isolated from non-cancerous surgical specimen were co-cultured with HCV-related proteins (Core, NS3, NS4, and NS5), and production of cytokines (TNF-α, IL-1β, and IL-10) and hydrogen peroxide were assessed. Furthermore, effects of neutralization antibodies against the TLR2, TLR3, or TLR4, and cytochalasin B on the production TNF-α by KCs were investigated.

Results

Kupffer cells produced markedly a proinflammatory cytokine TNF-α by stimulation with all HCV-related proteins studied, and values were as same as production by KCs stimulated with LPS. Importantly, this production in the case of NS3 was significantly blunted by about 60% by neutralization antibodies against the TLR4, but not cytochalasin B. Production of TNF-α by isolated KCs stimulated with LPS was significantly greater in the HCV-infected livers than the HCV/HBV-negative livers.

Conclusions

These results indicated that HCV-related proteins may cause prolonged activation of KCs in the HCV-infected liver, leading to accumulation of inflammatory cytokines that contribute to DNA damage and carcinogenesis. Furthermore, function of KCs was difference between patients infected with and without HCV infection.

Kiyosawa K, Tanaka E. Characteristics of hepatocellular carcinoma in Japan. Oncology. 2002;62(1):5–7.PubMedCrossRef

Yoshizawa H. Hepatocellular carcinoma associated with hepatitis C Virus infection in Japan: projection to other countries in the foreseeable future. Oncology. 2002;62(Suppl 1):8–17.PubMedCrossRef

Tanaka Y, Hanada K, Mizokami M, et al. Inaugural article: a comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades. Proc Natl Acad Sci USA. 2002;99:15584–15589.PubMedCrossRef

McGuinness PH, Painter D, Davies S, McCaughan GW. Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection. Gut. 2000;46:260–269.PubMedCrossRef

Maki A, Kono H, Gupta M, et al. Predictive power of biomarkers of oxidative stress and inflammation in patients with hepatitis C virus-associated hepatocellular carcinoma. Ann Surg Oncol. 2007;14:1182–1190.PubMedCrossRef

Matsumoto K, Satoh Y, Sugo H, et al. Immunohistochemical study of the relationship between 8-hydroxy-2′-deoxyguanosine levels in noncancerous region and postoperative recurrence of hepatocellular carcinoma in remnant liver. Hepatol Res. 2003;25:435–441.PubMedCrossRef

Burgio VL, Ballardini G, Artini M, Caratozzolo M, Bianchi FB, Levrero M. Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of hepatitis C virus stiology. Hepatology. 1998;27:1600–1606.PubMedCrossRef

Wheeler MD, Kono H, Yin M, et al. The role of Kupffer cell oxidant production in early ethanol-induced liver disease. Free Radic Biol Med. 2001;31:1544–1549.PubMedCrossRef

Rusyn I, Kadiiska MB, Dikalova A, et al. Phthalates rapidly increase production of reactive oxygen species in vivo: role of Kupffer cells. Mol Pharmacol. 2001;59:744–750.PubMed

10.

Dolganiuc A, Oak S, Kodys K, et al. Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterology. 2004;127:1513–1524.PubMedCrossRef

11.

Dolganiuc A, Kodys K, Kopasz A, et al. Hepatitis C virus core and nonstructural protein 3 proteins induce pro-and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J Immunol. 2003;170:5615–5624.PubMed

12.

Chang S, Dolganiuc A, Szabo G. Toll-like receptors 1 and 6 are involved in TLR2-mediated macrophage activation by hepatitis C virus core and NS3 proteins. J Leukoc Biol. 2007;82:479–487.PubMedCrossRef

13.

Heuff G, Meyer S, Beelen RHJ. Isolation of rat and human Kupffer cells by a modified enzymatic assay. J Immunol Meth. 1994;174:61–65.CrossRef

14.

Decker K. Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem. 1990;192:245–261. Review.PubMedCrossRef

15.

Pileri P, Uematsu Y, Campagnoli S, et al. Binding of hepatitis C virus to CD81. Science. 1998;282:938–941.PubMedCrossRef

16.

Zeisel MB, Koutsoudakis G, Schnober EK, et al. Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81. Hepatology. 2007;46:1722–1731.PubMedCrossRef

17.

Muriel P, Alba N, Perez-Alvarez VM, Shibayama M, Tsutsumi VK. Kupffer cells inhibition prevents hepatic lipid peroxidation and damage induced by carbon tetrachloride. Comp Biochem Physiol C Toxicol Pharmacol. 2001;130:219–226.PubMedCrossRef

18.

Niemela O, Parkkila S, Bradford B, Iimuro Y, Pasanen M, Thurman RG. Effect of Kupffer cell inactivation on ethanol-induced protein adducts in the liver. Free Radic Biol Med. 2002;33:350–355.PubMedCrossRef

19.

Michael SL, Pumford NR, Mayeux PR, Niesman MR, Hinson JA. Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species. Hepatology. 1999;30:186–195.PubMedCrossRef

20.

Ju C, Reilly TP, Bourdi M, et al. Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice. Chem Res Toxicol. 2002;15:1504–1513.PubMedCrossRef

21.

Schwabe RF, Brenner DA. Mechanisms of liver injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol. 2006;290:583–589.CrossRef

22.

Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005;120:649–661.PubMedCrossRef

23.

Pham CG, Bubici C, Zazzeroni F, et al. Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell. 2004;119:529.PubMedCrossRef

24.

Asakawa M, Kono H, Amemiya H, et al. Role of interleukin-18 and its receptor in hepatocellular carcinoma associated with hepatitis C virus infection. Int J Cancer. 2006;118:564–570.PubMedCrossRef

25.

Zhang H-Y, Nanji AA, Luk JM, et al. Macrophage migration inhibitory factor expression correlates with inflammatory changes in human chronic hepatitis B infection. Liver Int. 2005;25:571–579.PubMedCrossRef

26.

Kallinowski B, Haseroth K, Marinos G, et al. Induction of tumour necrosis factor (TNF) receptor type p55 and p75 in patients with chronic hepatitis C virus (HCV) infection. Clin Exp Immunol. 1998;111:269–277.PubMedCrossRef

27.

Farinati F, Cardin R, Bortolami M, Guido M, Rugge M. Oxidative damage, pro-inflammatory cytokines, TGF-alpha and c-myc in chronic HCV-related hepatitis and cirrhosis. World J Gastroenterol. 2006;12:2065–2069.PubMed

28.

Tomita M, Yamamoto K, Kobashi H, Ohmoto M, Tsuji T. Immunohistochemical phenotyping of liver macrophages in normal and diseased human liver. Hepatology. 1994;20:317–325.PubMedCrossRef

29.

Dolganiuc A, Garcia C, Kodys K, Szabo G. Distinct Toll-like receptor expression in monocytes and T-cells in chronic HCV infection. World J Gastroenterol. 2006;12:1198–1204.PubMed

30.

Lin RS, Lee FY, Lee SD, et al. Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. J Hepatol. 1995;22:165–172.PubMedCrossRef

31.

Plachouras D, Stamatakos M, Baziaka F, et al. Portal and systemic endotoxemia in abdominal operations: the significance of acute abdomen. J Surg Res. 2006;134:133–137.PubMedCrossRef

Titel: HCV-Related Proteins Activate Kupffer Cells Isolated from Human Liver Tissues
verfasst von: Naohiro Hosomura
Hiroshi Kono
Masato Tsuchiya
Kenichi Ishii
Masahito Ogiku
Masanori Matsuda
Hideki Fujii
Publikationsdatum: 01.04.2011
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 4/2011
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-010-1395-y

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2011

Riboflavin Depletion Impairs Cell Proliferation in Adult Human Duodenum: Identification of Potential Effectors

Gastric Emptying of Solids and Liquids for Evaluation for Gastroparesis

Accuracy of MELD Scores in Predicting Mortality in Decompensated Cirrhosis from Variceal Bleeding, Hepatorenal Syndrome, Alcoholic Hepatitis, or Acute Liver Failure As Well As Mortality After Non-transplant Surgery or TIPS

Adverse Effects of Long-Term Proton Pump Inhibitor Therapy

Altered Gut Flora Are Associated with Septic Complications and Death in Critically Ill Patients with Systemic Inflammatory Response Syndrome

The Expression of PTHLH in Human Gastric Mucosa Enterochromaffin-Like Cells