bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guanine and Plasmid DNA binding of Mono‐ and Trinuclear fac‐[Re(CO)3]+ Complexes with Amino Acid Ligands
Authors: Zobi Fabio , Spingler Bernhard , Alberto Roger 
Published: June 2005

AbstractWe have synthesized and fully characterized four new complexes comprising the fac‐[Re(CO)3]+ moiety and the ligands NH3, L‐proline (Pro), or N,N‐dimethylglycine (dmGly). The reaction of [Re(H2O)3(CO)3]+ with the two amino acids gives trinuclear complexes of general formula [Re(L)(CO)3]3 (where L=amino acid). We have studied the in vitro behavior of these compounds with guanine and DNA in order to understand whether the cytotoxicity exhibited by certain rhenium complexes based on the fac‐[Re(CO)3]+ core is due to the formation of nucleobase complexes and inter‐ or intrastrand links between DNA bases. We have performed model studies with guanine and studied the structural effects induced by different rhenium(I) tricarbonyl complexes on ΦX174 plasmid DNA by electrophoretic methods. Our results show that rhenium complexes with two available coordination sites interact with plasmid DNA to form a stable adduct that is likely to involve two bases.
Monophosphite Ligands Derived from Carbohydrates and H8‐BINOL: Highly Enantioselective Rh‐Catalyzed Asymmetric Hydrogenations.
Authors: Huang Hanmin , Liu Xiongcai , Chen Huilin , Zheng Zhuo 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Chiral C2‐Symmetric Ligands Containing Two Binaphthyl Units Linked by 2,2′‐Bipyridyl Bridge in Asymmetric Catalysis.
Authors: Bai Xiao‐Li , Kang Chuan‐Qing , Liu Xu‐Dong , Gao Lian‐Xun 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Bromoallenes as Allyl Dication Equivalents in the Absence of Palladium(0): Synthesis of Bicyclic Sulfamides by Tandem Cyclization of Bromoallenes.
Authors: Hamaguchi Hisao , Kosaka Shohei , Ohno Hiroaki , Tanaka Tetsuaki 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Novel and Direct Oxidative Cyanation Reactions of Heteroaromatic Compounds Mediated by a Hypervalent Iodine(III) Reagent.
Authors: Dohi Toshifumi , Morimoto Koji , Kiyono Yorito , Tohma Hirofumi , Kita Yasuyuki 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
A Facile and Practical Method for the Preparation of Thioacetates from Alkyl Halides and Sodium Thioacetate Catalyzed by PEG400.
Authors: Cao Yu‐Qing , Du Yun‐Fei , Chen Bao‐Hua , Dai Zhi 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
A Convenient Synthesis of Functionalized 1‐Aryl‐1,3‐alkadiynes.
Authors: Balova Irina A. , Sorokoumov Victor N. , Morozkina Svetlana N. , Vinogradova Olga V. , Knight David W. , Vasilevsky Sergey F. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Highly Diastereoselective Allylic Azide Formation and Isomerization. Synthesis of 3(2′‐Amino)‐β‐lactams.
Authors: Cardillo Giuliana , Fabbroni Serena , Gentilucci Luca , Perciaccante Rossana , Piccinelli Fabio , Tolomelli Alessandra 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Samarium Diiodide Promoted Generation and Asymmetric Hydroxyalkylation of N,O‐Diprotected (3S)‐3‐Pyrrolidinol 2‐Carbanions.
Authors: Zheng Xiao , Feng Chen‐Guo , Ye Jian‐Liang , Huang Pei‐Qiang 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
A Novel Spiroheterocyclization: Synthesis of 1‐Ethoxycarbonylmethylidene‐8‐ (2′‐ethoxycarbonylmethylidene‐5′,5′‐dimethyl‐3′‐pyrrolidinylidene) ‐3,3,6‐trimethyl‐2‐azaspiro[4,5]deca‐6,9‐diene.
Authors: Shklyaev Yu. V. , Nifontov Yu. V. , Kodess M. I. , Ezhikova M. A. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Derivatives of Indole. Part 143. Synthesis of Photochromic Derivatives of 2‐Arylindoles.
Authors: Gogrichiani E. O. , Katsadze E. A. , Gavtadze N. G. , Samsoniya Sh. A. , Duerr H. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Polyfunctional Pyrazoles. Part 3. Synthesis of 3‐(3‐Aryl‐4‐formyl‐1‐pyrazolyl)propionic Acids and Their Amides.
Authors: Bratenko M. K. , Chornous V. A. , Vovk M. V. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis, Characterization, and Structural Investigations of 1‐Amino‐3‐substituted‐1,2,3‐triazolium Salts, and a New Route to 1‐Substituted‐1,2,3‐triazoles.
Authors: Kaplan Greg , Drake Greg , Tollison Kerri , Hall Leslie , Hawkins Tommy 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Efficient Syntheses of 5‐Aminoalkyl‐1H‐tetrazoles and of Polyamines Incorporating Tetrazole Rings.
Authors: Athanassopoulos Constatinos M. , Garnelis Thomas , Vahliotis Dimitrios , Papaioannou Dionissios 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Stereospecific Synthesis of 2,2,3‐Trisubstituted Tetrahydroquinolines: Application to the Total Syntheses of Benzastatin E and Natural Virantmycin.
Authors: Ori Mayuko , Toda Narihiro , Takami Kazuko , Tago Keiko , Kogen Hiroshi 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Solvent‐Free Microwave Synthesis of Bis‐pyrazolo[3,4‐b:4′,3′‐e]pyridines and Study of Their Antifungal Properties.
Authors: Quiroga J. , Portilla J. , Insuasty B. , Abonia R. , Nogueras M. , Sortino M. , Zacchino S. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Design and Synthesis of Novel 9‐Substituted‐7‐aryl‐3,4,5,6‐tetrahydro‐2H‐pyrido[4,3‐b]‐ and [2,3‐b]‐1,5‐oxazocin‐6‐ones as NK1 Antagonist.
Authors: Seto Shigeki , Tanioka Asao , Ikeda Makoto , Izawa Shigeru 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Oxidation of o‐Isopropylphenol with Lead Tetraacetate: Synthesis of the Unit of Celastroidin Terpenes by the Diels—Alder Condensation.
Authors: Jankowski C. K. , Savoie A. , Lesage D. , Boivin J. , Leclaire G. , Diaz T. E. , Reyes‐Chilpa R. , Jimenez‐Estrada M. , Barrios H. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Complanadine B, Obscurumines A and B, New Alkaloids from Two Species of Lycopodium
Authors: Morita Hiroshi , Ishiuchi Kan'ichiro , Haganuma Asami , Hoshino Tomohiro , Obara Yutaro , Nakahata Norimichi , Kobayashi Jun'ichi 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Monoamine Transporter Affinity of New 2β‐Carbomethoxy‐3β‐[4‐(substituted thiophenyl)]phenyltropanes: Discovery of a Selective SERT Antagonist with Picomolar Potency.
Authors: Tamagnan Gilles , Alagille David , Fu Xing , Kula Nora S. , Baldessarini Ross J. , Innis Robert B. , Baldwin Ronald M. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Antibacterial Activity of 1‐[1,2,4‐Triazol‐3‐yl] and 1‐[1,3,4‐Thiadiazol‐2‐yl]‐3‐methylthio‐6,7‐dihydrobenzo [c]thiophen‐4(5H)ones.
Authors: Tehranchian Sara , Akbarzadeh Tahmineh , Fazeli Mohammad Reza , Jamalifar Hossein , Shafiee Abbas 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
New Heterocyclic Ligands for the Adenosine Receptors P1 and for the ATP Receptors P2
Authors: Baraldi Pier Giovanni , Romagnoli Romeo , Tabrizi Mojgan Aghazadeh , Bovero Andrea , Preti Delia , Fruttarolo Francesca , Moorman Allan R. , Borea Pier Andrea 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Biaryls and Heterobiaryls as α‐Glucosidase and Protein Tyrosine Phosphatase Inhibitors.
Authors: Sharon Ashoke , Pratap Ramendra , Tripathi Brajendra , Srivastava A. K. , Maulik P. R. , Ram Vishnu Ji 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Studies on Novel Synthetic Methodologies. Part 39. Simple, Mild and Efficient Thioacetalization and Transthioacetalization of Carbonyl Compounds and Deprotection of Thioacetals: Unique Role of Thiols in the Selectivity of Thioacetalization.
Authors: Das Biswanath , Ramu Ravirala , Reddy Majjigapu Ravinder , Mahender Gurram 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Efficient Cleavage of Carboxylic tert‐Butyl and 1‐Adamantyl Esters, and N‐Boc‐Amines Using H2SO4 in CH2Cl2.
Authors: Strazzolini Paolo , Misuri Nazareno , Polese Pierluigi 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Buchwald—Hartwig Aminations of Aryl Chlorides: A Practical Protocol Based on Commercially Available Pd(0)‐NHC Catalysts.
Authors: Goossen L. J. , Paetzold J. , Briel O. , Rivas‐Nass A. , Karch R. , Kayser B. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Nucleophilic Vinylic Substitutions of (Z)‐(2‐Aroyloxyvinyl)phenyl‐λ3‐iodanes with Tetrabutylammonium Halides: Vinylic SN2 Reactions and Ligand Coupling on Iodine(III).
Authors: Ochiai Masahito , Nishi Yoshio , Hirobe Masaya 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Nucleophilic Aromatic Substitution on 4‐Fluorophenylsulfonamides: Nitrogen, Oxygen, and Sulfur Nucleophiles.
Authors: Badetti Elena , Moreno‐Manas Marcial , Pleixats Roser , Sebastian Rosa M. , Serra Anna , Soler Roger , Vallribera Adelina 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Suzuki—Miyaura Cross‐Coupling Reaction of Aryl Bromides and Chlorides with Phenylboronic Acid under Aerobic Conditions Catalyzed by Palladium Complexes with Thiosemicarbazone Ligands.
Authors: Kostas Ioannis D. , Andreadaki Fotini J. , Kovala‐Demertzi Dimitra , Prentjas Christos , Demertzis Mavroudis A. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Reduction versus Rearrangement of 6,13‐Dihydro‐6,13‐diarylpentacene‐6,13‐diols Affording 6,13‐ and 13,13′‐Substituted Pentacene Derivatives.
Authors: Vets Nathalie , Smet Mario , Dehaen Wim 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
The Halogen—Lithium Exchange Reaction of 3,3‐Dichloro‐2‐azetidinones: Application to the Synthesis of cis‐4‐Aryl‐3‐chloro‐2‐azetidinones.
Authors: Dejaegher Yves , Denolf Bram , Stevens Christian V. , De Kimpe Norbert 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
cis‐6‐Oxo‐hexahydro‐2‐oxa‐1,4‐diazapentalene and cis‐6‐Oxo‐Hexahydropyrrolo[3,2‐c]pyrazole Based Scaffolds: Design, Rationale, Synthesis and Cysteinyl Proteinase Inhibition.
Authors: Wang Yikang , Benn Alex , Flinn Nick , Monk Tracy , Ramjee Manoj , Watts John , Quibell Martin 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Baker′s Yeast‐Mediated Regioselective Reduction of 2,4‐Dinitroacylanilines: Synthesis of 2‐Substituted 6‐Nitrobenzimidazoles.
Authors: Olguin Luis F. , Jimenez‐Estrada Manuel , Barzana Eduardo , Navarro‐Ocana Arturo 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Three‐Component Reactions of Halogenotrinitromethanes with Alkenes.
Authors: Budynina Ekaterina M. , Ivanova Olga A. , Averina Elena B. , Grishin Yurii K. , Kuznetsova Tamara S. , Zefirov Nikolai S. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
One‐Pot Stereoselective Synthesis of Pyrano[3,2‐c]benzothiopyrans: A New Generation and [4 + 2] Cycloaddition of ortho‐Thioquinonemethides.
Authors: Inoue Seiichi , Wang Ping , Nagao Mami , Hoshino Yujiro , Honda Kiyoshi 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis of 3‐Chloro‐6,6‐diphenyl‐6,11‐dihydropyrido[1′,2′:1,2]imidazo [4,5‐b]quinoline Based on Reaction of 2‐Chloromethyl‐4,4‐diphenyl‐4H‐3,1‐benzoxazine with 2‐Amino‐5‐chloropyridine.
Authors: Gromachevskaya E. V. , Krapivin G. D. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Benzo[h][1,6]naphthyridines from Dimethyl 1,2‐Dihydro‐2‐(2‐nitrophenyl)‐pyridine‐3,5‐dicarboxylate.
Authors: Goerlitzer K. , Bode M. , Jones P. G. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Novel and Orally Bioavailable Inducible Nitric Oxide Synthase Inhibitors. Synthesis and Evaluation of Optically Active 4,5‐Dialkyl‐2‐iminoselenazolidine Derivatives.
Authors: Ueda Shigeo , Terauchi Hideo , Suzuki Kenji , Yano Akihiro , Matsumoto Masashi , Kubo Taeko , Minato Hisao , Arai Yukiyo , Tsuji Jun‐ichi , Watanabe Nobuhide 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Covalent Binding of Modified Nucleic Acids to Proteins as a Method for Investigation of Specific Protein—Nucleic Acid Interactions
Authors: Zatsepin T. S. , Dolinnaya N. G. , Kubareva E. A. , Ivanovskaya M. G. , Metelev V. G. , Oretskaya T. S. 
Published: June 2005

AbstractFor Abstract see ChemInform Abstract in Full Text.
Detection of electrical tree propagation by partial discharge measurements
Authors: Vogelsang R. , Fruth B. , Farr T. , Fröhlich K. 
Published: June 2005

AbstractThe partial discharge (PD) activity during propagation of electrical treeing in epoxy resin is described. The electrical trees grew in needle‐plane samples without and with an internal barrier up to the final breakdown. The simultaneous tree growth and discharge activity show a correlation between the propagation state of the tree and the thereby measured PD. Especially, the changes in the tree structure can clearly be detected. Based on these characteristics a new model describing tree growth is presented. It appears that measurements from machine insulation can be interpreted in terms of the PD pattern. Copyright © 2005 John Wiley & Sons, Ltd.
Stray load loss analysis of induction motors due to harmonic electromagnetic fields of stator and rotor
Authors: Yamazaki Katsumi 
Published: June 2005

AbstractIn this paper, we investigate the stray load losses of induction motors due to the harmonic magnetic fields caused by the stator and the rotor slot ripples. The nonlinear time‐stepping finite element analysis considering end‐effects of the motor is carried out to obtain the copper losses of the stator winding and the rotor cage. The core losses of the stator and the rotor are calculated from the time‐variation of the magnetic field distribution obtained by the finite element analysis. It is clarified that the stator and the rotor core losses increase due to the load, which can be considered as the main part of the stray load loss. Copyright © 2005 John Wiley & Sons, Ltd.
A Viral Kinetic Study Using Pegylated Interferon Alfa-2b and/or Lamivudine in Patients With Chronic Hepatitis B/HBeAg Negative *
Authors: Sypsa Vassiliki-Anastasia , Mimidis Konstantinos , Tassopoulos Nicholas C. , Chrysagis Dimitrios , Vassiliadis Themistoklis , Moulakakis Antonios , Raptopoulou Maria , Haida Caterina , Hatzakis Angelos 
Published: June 2005

Abstract

We studied viral dynamic parameters in 44 chronic hepatitis B/hepatitis B e antigen (HBeAg)(−) patients treated with pegylated interferon alfa-2b (PEG-IFN) 100 or 200 μg weekly or lamivudine 100 mg daily or the combination of PEG-IFN 100 or 200 μg with lamivudine. Patients receiving PEG-IFN monotherapy exhibited viral load oscillations between weekly injections, which were resolved by the addition of lamivudine. The median pharmacological delay was estimated at 4.1, 5.8, and 1.8 hours in PEG-IFN monotherapy, PEG-IFN 100/200 μg + lamivudine, and lamivudine monotherapy, respectively (

P

= .44). The median half-life of free virus was 12.7 hours (range, 2.4-69.2 hours). The mean antiviral effectiveness of PEG-IFN 100/200 μg monotherapy was lower than that of lamivudine (82.6% vs. 96.4%;

P

= .005). The mean effectiveness of PEG-IFN 100 μg + lamivudine and PEG-IFN 200 μg + lamivudine was 92.8% and 94.4%, respectively. The half-life of infected cells ranged from 2.7 to 75 days. The median half-life of infected cells in patients receiving the combination regimens of PEG-IFN and lamivudine was similar to that of lamivudine patients (5.0 days vs. 6.0 days,

P

= .77).
In conclusion
, the addition of pegylated interferon alfa-2b in lamivudine treatment was found to neither enhance the potency of blocking HBV production nor the decay rates of infected cells.

Supplementary material for this article can be found on the Hepatology website

(
http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html
). (Hepatology 2005;42:77–85.)
Ischemia/Reperfusion Accelerates the Outgrowth of Hepatic Micrometastases in a Highly Standardized Murine Model *
Authors: van der Bilt Jarmila D. W. , Kranenburg Onno , Nijkamp Maarten W. , Smakman Niels , Veenendaal Liesbeth M. , te Velde Elisabeth A. , Voest Emile E. , van Diest Paul J. , Borel Rinkes Inne H. M. 
Published: June 2005

Abstract

Mortality in colorectal cancer is associated with the development of liver metastases. Surgical removal of these tumors is the only hope for cure, but recurrence is common. During liver surgery, ischemia/reperfusion (I/R) often occurs as a result of hemorrhage or vascular clamping. Although the adverse effects of I/R on postoperative liver function are well documented, the influence of I/R on the outgrowth of residual micrometastases is unknown. We used a highly standardized mouse model of partial hepatic I/R to study the effects of I/R on the outgrowth of preestablished colorectal micrometastases. Five days following intrasplenic injection of C26 colon carcinoma cells, the vascular structures of the left lobe were clamped for 45 minutes under hemodynamically stable conditions. Tissue glutathione, plasma liver enzymes, hepatocellular necrosis, and tumor growth were assessed over time. I/R caused oxidative stress and early liver tissue damage. The outgrowth of micrometastases in occluded liver lobes was accelerated five- to sixfold compared with nonoccluded lobes and was associated with areas of necrotic liver tissue surrounded by inflammatory cells and apoptotic hepatocytes. Accelerated tumor growth and tissue necrosis were completely prevented by occluding blood flow intermittently. In contrast, ischemic preconditioning or treatment with the antioxidants α-tocopherol or ascorbic acid failed to protect against late tissue necrosis and tumor growth, although early hepatocellular damage was largely prevented by these methods.
In conclusion
, I/R is a strong stimulus of recurrent intrahepatic tumor growth. Measures to prevent I/R-induced late tissue necrosis cross-protect against this phenomenon. (Hepatology 2005;42:165–175.)
Comprehensive Analyses of CD8+ T Cell Responses During Longitudinal Study of Acute Human Hepatitis C *
Authors: Cox Andrea L. , Mosbruger Timothy , Lauer Georg M. , Pardoll Drew , Thomas David L. , Ray Stuart C. 
Published: June 2005

Abstract

We comprehensively studied the cellular immune response during acute human hepatitis C virus (HCV) infection by monthly prospective sampling of persons at high risk of infection. In 19 of 23 subjects, interferon-gamma–secreting T cells specific for 1 or more peptides spanning the entire HCV polyprotein were detected 1 to 3 months after infection. The median time to development of interferon gamma responses to HCV peptides was 33 days (range, 29-50 days), and these responses peaked between 180 and 360 days. Nineteen subjects had sufficient follow-up to determine outcome, with 15 (79%) developing persistent viremia and 4 (21%) clearing viremia spontaneously. Of those with progression to chronic infection and detectable T cell responses, all lost recognition of one or more antigens recognized during acute infection, and the median reduction in the magnitude of responses was 85%. Most significantly, despite ongoing viremia, those who had persistent infection did not develop new epitope specificities after the first 6 months of infection.
In conclusion
, in most individuals, the CD8+ T cell responses generated early in HCV infection decline in peripheral blood and are not replaced with new responses.

Supplementary material for this article can be found on the Hepatology website

(
http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html
). (Hepatology 2005;42:104–112.)
Steatosis: Co-factor in Other Liver Diseases *
Authors: Powell Elizabeth E. , Jonsson Julie R. , Clouston Andrew D. 
Published: June 2005

Abstract

The prevalence of fatty liver is rising in association with the global increase in obesity and type 2 diabetes. In the past, simple steatosis was regarded as benign, but the presence of another liver disease may provide a synergistic combination of steatosis, cellular adaptation, and oxidative damage that aggravates liver injury. In this review, a major focus is on the role of steatosis as a co-factor in chronic hepatitis C (HCV), where the mechanisms promoting fibrosis and the effect of weight reduction in minimizing liver injury have been most widely studied. Steatosis, obesity, and associated metabolic factors may also modulate the response to alcohol- and drug-induced liver disease and may be risk factors for the development of hepatocellular cancer. The pathogenesis of injury in obesity-related fatty liver disease involves a number of pathways, which are currently under investigation. Enhanced oxidative stress, increased susceptibility to apoptosis, and a dysregulated response to cellular injury have been implicated, and other components of the metabolic syndrome such as hyperinsulinemia and hyperglycemia are likely to have a role. Fibrosis also may be increased as a by-product of altered hepatocyte regeneration and activation of bipotential hepatic progenitor cells.
In conclusion
, active management of obesity and a reduction in steatosis may improve liver injury and decrease the progression of fibrosis. (Hepatology 2005;42:5–13.)
Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *
Authors: Wiegard Christiane , Frenzel Christian , Herkel Johannes , Kallen Karl-Josef , Schmitt Edgar , Lohse Ansgar W. 
Published: June 2005

Abstract

CD4+CD25+ regulatory T cells (Treg) are important mediators of peripheral immune tolerance; however, whether Treg participate also in hepatic immune tolerance is not clear. Therefore, we tested the potential of Treg to suppress stimulation of CD4+ T cells by liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC), or hepatocytes. In the absence of Treg, all 3 types of liver cells could stimulate CD4+ T cell proliferation; in the presence of Treg, however, CD4+ T cell proliferation was suppressed. Interaction with KC even stimulated the expansion of the Treg population; LSEC or hepatocytes, in contrast, could not induce proliferation of Treg. Because liver inflammation can be induced by infection, we tested the potential of liver cells to modify Treg suppressor activity in the presence of microbial signals. In the presence of immune-stimulatory CpG-oligonucleotides, LSEC, KC, and hepatocytes could indeed overcome Treg-mediated suppression; in the presence of lipopolysaccharide (LPS), however, only KC and hepatocytes, but not LSEC, could overcome Treg suppressor activity. Hepatocytes from mice with deficient toll-like receptor-4 signaling failed to abrogate Treg suppression in response to LPS, indicating that overcoming Treg suppressor activity was indeed a response of the liver cell and not of the Treg.
In conclusion
, Treg can suppress CD4+ T cell stimulation by liver cells. However, in response to microbial signals, the liver cells can overcome the suppressive activity of Treg. Thus, liver cells may facilitate the transition from hepatic immune tolerance to hepatic inflammation by controlling Treg suppressor activity. (Hepatology 2005;42:193–199.)