Serum from HCC patients contained higher concentration TGF-β1 than those from cirrhosis and healthy control. Flow cytometry indicated that blocking TGF-β1 stimulated HCC cells proliferation and knockdown it leaded to G1 arrest. Colony formation assay displayed that silencing TGF-β1 affect proliferation of cancer cells. And animal experiments showed that interference TGF-β1 decreased the metastatic nodules in lungs.

Conclusion: Cancer secreted-TGF-β1 is necessary for proliferation of HCC cells. Knockdown selleck chemicals TGF-β1 could inhibit tumor growth and decrease metastases. The findings suggest that TGF-β1 could be a potential therapeutic target for HCC treatment. Key Word(s): 1. HCC; 2. TGF-β1; 3. metastasis; Presenting Author: HIROKI UCHIDA Additional Authors: YUKIO IWASHITA, KIMINORI WATANABE, TAKAHIDE KAWASAKI, YUICHIRO KAWANO, YOKO KOMORI, KAZUHIRO YADA, MASAYUKI OHTA, SEIGO KITANO Corresponding Author: HIROKI UCHIDA Affiliations: Oita university Objective: Surgical resection for hepatocellular carcinoma (HCC) is regarded as a curable treatment. A tumor adhering to the major hepatic vessels sometimes causes a need to perform hepatectomy without surgical margin. The aim of this study was to evaluate the short-term

outcomes HDAC inhibitors list of hepatectomy with null surgical margin for HCC. Methods: rom January 2010 to December 2012, 70 patients who underwent curative hepatectomy for HCC in Oita University were analyzed. They were divided into two group with null margin group and negative margin group. These two groups were compared in terms of clinicopathological characteristics, perioperative features, and short-term outcomes. Etomidate Results: Nineteen patients (27.1%) had been performed hepatectomy with null margin diagnosed pathologically. Mean intraoperative

blood loss was greater and operation time was longer in the null margin group as compared to those in the negative margin group. There were no significant differences in overall survival, disease free survival and other clinicopathological features between the two groups. In the null margin group, 12 patients had recurrence (59.1%) and the recurrence site was liver in all the patients. Four of the 12 patients (33%) had recurrence at the resected stump of the liver and the mean period of recurrence was 10.8 months. Conclusion: Hepatectomy with null surgical margin for HCC is technically demanding. It would lead to comparable and adequate surgical outcomes in patients with tumors in contact with major vessels, compared to hepatectomy with negative surgical margin. Key Word(s): 1. HCC; 2.

Serum from HCC patients contained higher concentration TGF-β1 than those from cirrhosis and healthy control. Flow cytometry indicated that blocking TGF-β1 stimulated HCC cells proliferation and knockdown it leaded to G1 arrest. Colony formation assay displayed that silencing TGF-β1 affect proliferation of cancer cells. And animal experiments showed that interference TGF-β1 decreased the metastatic nodules in lungs.

Conclusion: Cancer secreted-TGF-β1 is necessary for proliferation of HCC cells. Knockdown Adriamycin order TGF-β1 could inhibit tumor growth and decrease metastases. The findings suggest that TGF-β1 could be a potential therapeutic target for HCC treatment. Key Word(s): 1. HCC; 2. TGF-β1; 3. metastasis; Presenting Author: HIROKI UCHIDA Additional Authors: YUKIO IWASHITA, KIMINORI WATANABE, TAKAHIDE KAWASAKI, YUICHIRO KAWANO, YOKO KOMORI, KAZUHIRO YADA, MASAYUKI OHTA, SEIGO KITANO Corresponding Author: HIROKI UCHIDA Affiliations: Oita university Objective: Surgical resection for hepatocellular carcinoma (HCC) is regarded as a curable treatment. A tumor adhering to the major hepatic vessels sometimes causes a need to perform hepatectomy without surgical margin. The aim of this study was to evaluate the short-term

outcomes GSI-IX of hepatectomy with null surgical margin for HCC. Methods: rom January 2010 to December 2012, 70 patients who underwent curative hepatectomy for HCC in Oita University were analyzed. They were divided into two group with null margin group and negative margin group. These two groups were compared in terms of clinicopathological characteristics, perioperative features, and short-term outcomes. Casein kinase 1 Results: Nineteen patients (27.1%) had been performed hepatectomy with null margin diagnosed pathologically. Mean intraoperative

blood loss was greater and operation time was longer in the null margin group as compared to those in the negative margin group. There were no significant differences in overall survival, disease free survival and other clinicopathological features between the two groups. In the null margin group, 12 patients had recurrence (59.1%) and the recurrence site was liver in all the patients. Four of the 12 patients (33%) had recurrence at the resected stump of the liver and the mean period of recurrence was 10.8 months. Conclusion: Hepatectomy with null surgical margin for HCC is technically demanding. It would lead to comparable and adequate surgical outcomes in patients with tumors in contact with major vessels, compared to hepatectomy with negative surgical margin. Key Word(s): 1. HCC; 2.

Conclusion: There is only poor to moderate correlation between 2D and 3D manometry findings. Even in patients with normal pressure values for RP and SP, there is a high possibility of detecting abnormalities in the 3DPP. Key Word(s): 1. 3 Dimensional; GS-1101 cost 2. Anorectal manomtry; Presenting Author: DAKSHITHA WICKRAMASINGHE Additional Authors: SUPUN SENARATNE, CHAMILA PERERA, NANDADEVA SAMARASEKERA Corresponding Author: DAKSHITHA WICKRAMASINGHE Affiliations: none Objective: Stoma care is a specialized area in nursing but in Sri Lanka, there

were only a handful of trained stoma care nurses. In June 2012, the Ministry of Health conducted a 4 week full time course in Stoma Therapy for nurses. Methods: Participants completed a questionnaire derived from a validated questionnaire used in a previous publication, which evaluated basic demographic Erlotinib details and some aspects of patient care. The questionnaire was administered on the 1st day of the program and at the completion. Data were analyzed using Wilcoxon signed-rank test. Results: There were 24 males and 37 females. The mean age was 31.5 (± 5.5) years. All participants completed the questionnaire. The

mean years in nursing was 9.5 (± 5.5) years. All 15 domains of patient care had improved at the end of the program (Biggest increase was seen in staff confidence category (average increase in score 63.5%)). The 3 domains that had the biggest improvement in descending order are; the confidence to select different appliances to suit different conditions (Z = −6.638, P < 0.0001), having material for proper patient

teaching (Z = −6.323, P < 0.001) and confidence in educating patients (Z = −6.544, P < 0.001). Our results suggest that a 4 week course provides adequate knowledge and confidence to function as stoma care nurses. The responses also indicates that the program was successful in making them confident in managing stoma patients and functioning independently and the program was successful in providing a comprehensive training and a holistic approach. Conclusion: A 4 week stoma care training program for trained nurses provides the participants GNA12 with the necessary knowledge and confidence to function independently. Programs of this nature can be conducted in developing countries with limited resources, using local resource personnel with minimal cost to the state. Key Word(s): 1. Stoma care nurse; 2. Training; 3. Developing country; 4. Effectiveness; Presenting Author: JIE HONG Additional Authors: YURONG WENG, YANAN YU, LINLIN REN, JING-YUAN FANG Corresponding Author: JIE HONG Affiliations: Gastroenterology Objective: c9orf140 is a novel gene that has been recently isolated and indentified by the mRNA differential display (mRNAD), which is associated with cell proliferation and tumorigenesis in Gastric caner. Moreover, it was reported that the expression of c9orf140 is significantly elevated in colorectal caner (CRC) tissues when compared with normal tissues.

“
“Epidemiological evidences suggested an inverse association between the use of glucosamine supplements and colorectal cancer (CRC) risk. In this study, the efficacy of glucosamine to attenuate dextran sodium sulfate (DSS)-induced colitis, a precancerous condition for CRC, was evaluated. C57BL/6 mice were separated into three groups receiving

glucosamine sulfate at concentrations of 0, 0.05, and 0.10% (w/w) of AIN-93G diet, respectively for 4 weeks. Colitis was induced by supplying two cycles (5 days per cycle) of 2% DSS in the animals’ drinking water. Glucosamine supplementation at the level of 0.10% of the diet (w/w) reduced colitis-associated symptoms as measured by disease activity index (DAI). SP600125 Tumor necrosis factor-α (TNF-α), interleukin-1β, and nuclear factor-kappa B mRNA expression in the Ribociclib in vitro colonic mucosa was significantly lower in animals fed 0.10% glucosamine compared with those of the control group. Expression of the tight junction proteins ZO-1 and occludin was significantly higher in the 0.10% glucosamine-supplemented group compared

with the other groups. Also, colonic protein expression of lipocalin 2, and serum concentrations of interleukin-8 and amyloid P component (SAP) were significantly reduced in the 0.10% glucosamine-supplemented group compared with the control group. These results suggest that glucosamine attenuates the colitis disease activity by suppressing NF-κB activation and related inflammatory responses. “
“Wayne State University, Detroit, MI Genentech, Inc. San Francisco, CA Institute of Pharmacology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany The role of organic anion transporting polypeptides (OATPs), particularly the members of OATP1B subfamily, in hepatocellular handling of endogenous and exogenous compounds is an important and emerging area of research. Using a mouse model lacking

Slco1b2, the murine ortholog of the OATP1B subfamily, we have demonstrated previously that genetic ablation causes reduced hepatic clearance capacity for substrates. In this study, we focused on the physiological function of the hepatic OATP1B transporters. RVX-208 First, we studied the influence of the Oatp1b2 deletion on bile acid (BA) metabolism, showing that lack of the transporter results in a significantly reduced expression of Cyp7a1, the key enzyme of BA synthesis, resulting in elevated cholesterol levels after high dietary fat challenge. Furthermore, Slco1b2−/− mice exhibited delayed clearance after oral glucose challenge resulting from reduced hepatic glucose uptake. In addition to increased hepatic glycogen content, Slco1b2−/− mice exhibited reduced glucose output after pyruvate challenge. This is in accordance with reduced hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK) in knockout mice.

Successful integration of the mutant PAP gene into the genome of transgenic petunia was confirmed by PCR and Southern blot analysis. Expression of the PAP gene was further confirmed by RT-PCR and Western blot analysis. These results were consistent with the assay of resistance to CMV. “
“This study was carried out to identify pathogenic bacteria and fungi on mistletoe (Viscum album L.) and investigate

their potential use in biological control of this parasitic plant. For this purpose, a total of 48 fungal find more isolate and 193 bacterial strains were isolated from contaminated V. album during the summers 2005–2006. The isolated bacterial strains and fungal isolates were identified by using the Sherlock Microbial Identification System (MIS; Microbial ID, Newark) and microscopic methods, respectively. The bacterial strains that induced hypersensitive reaction (HR) on tobacco (Nicotiana tabacum L.) and fungal isolates were tested for pathogenicity on young shoots of mistletoe by using injection

methods. The pathogenic bacterial strains and fungal isolates were also tested for their activity against mistletoe using spray methods. Five bacterial strains (two Burkholderia cepacia, one each of Bacillus megaterium, Bacillus pumilus and Pandoraea pulminicola) were HR and pathogenicity positive when injected but none of them when sprayed on mistletoe. When fungi were injected, 32 isolates were pathogenic but only thirteen when sprayed on mistletoe. Alternaria alternata VAŞ-202, learn more VAŞ-205, VAŞ-217 and Acremonium kiliense VA-11 fungal isolates were the most effective ones and caused strong disease symptoms on mistletoe. The present study is the first report on the efficiency of potential biocontrol agents against mistletoe in Turkey. “
“Asparagus spears are usually vulnerable to pathogenic micro-organisms. In this study, 217 pathogens were isolated from symptomatic Tacrolimus (FK506) asparagus, and one highly virulent fungus (designated

EXAP-08) isolated from the rotted asparagus spears in cold storage was characterized in detail. Koch’s postulates were checked through pathogenicity tests, indicating that EXAP-08 infection could cause reproducible rot symptoms similar to those observed on naturally infected asparagus spears, and the pathogenicity of EXAP-08 was also relatively higher than other Fusarium pathogens, especially at 4°C. Through morphological and molecular identification, EXAP-08 was characterized as Fusarium asiaticum. This identification was further confirmed by phylogenetic analysis with the Histone gene H3 of EXAP-08 and other Fusarium species. EXAP-08 also belongs to 3A-DON (3-acetyl-4-deoxynivalenol) chemo-type, and the mycotoxin was detected during the infection of plant, implying the potential risks of mycotoxin contamination in fresh crops infected by this pathogen. Thus, this emerging pathogen threatening edible safety of asparagus spears should deserve particular quarantine inspection in the future.

TGF-β is another major mediator of liver fibrogenesis.25 HuR silencing in the CFSC-8B cell line markedly reduced

up-regulation of col1a1, α-SMA, and TGF-β mRNA after TGF-β treatment (Fig. 8A). RIP-qPCR analysis showed that α-SMA and TGF-β, but not col1a1, were bound to HuR in TGF-β-stimulated cells (Fig. 8A). In HSCs, TGF-β also plays a major role in inhibiting proliferation in HSCs.26 TGF-β treatment decreased levels of the cell-cycle activators, cyclin D1 and B1, while increasing levels of the cell-cycle inhibitor, p21 (Supporting Fig. 7A,B). HuR knockdown abrogated the antiproliferative effects of TGF-β in primary HSCs from BDL mice (Supporting Fig. 7C) and in the CFSC-8B cell line (Fig. 8B). This

antiproliferative effect of TGF-β was likely the result of reduced p21 levels (Fig. 8C). RIP-qPCR showed that TGF-β treatment induced an hypoxia-inducible factor cancer increased binding of HuR to p21 while reducing the interaction of cyclin D1 and B1 mRNA with HuR (Fig. 8C). TGF-β treatment did not regulate HuR at mRNA and protein levels, unlike PDGF (Supporting Fig. 7D,E). However, TGF-β induced Barasertib clinical trial increased cytoplasmic localization of HuR, both in primary HSCs (Supporting Fig. 3G) and in the CFSC-8B cell line (Fig. 8D and Supporting Fig. 7F). This translocation is unlikely to be mediated by ERK, AKT, or LKB1, because TGF-β did not activate any of these kinases (Fig. 8E). However, TGF-β activated p38 MAPK (Fig. 8E), and inhibition of this pathway prevented TGF-β-induced HuR translocation (Fig. 8F). TGF-β did not affect phosphorylation at any of the eight residues that we previously tested for PDGF-induced translocation (data not shown), suggesting that TGF-β and PDGF mediate HuR translocation by different post-translational modifications. In summary, we found that the profibrogenic

and antiproliferative actions of TGF-β could be controlled by HuR-mediated regulation of critical genes. Liver fibrosis and cirrhosis result from the majority of chronic liver insults and represent a difficult clinical Protein kinase N1 challenge. Recent studies have shown that HuR regulates angiotensin II–induced kidney fibrosis27 and ventricular remodeling after myocardial infarction.28 However, HuR functions during liver fibrosis development are unknown. Several studies have shown that HuR regulates the expression of several mRNAs encoding proinflammatory cytokines (e.g., TNF-α, IL-6, TGF-β, and interferon-gamma), proinflammatory mediators (e.g., iNOS), and chemoattractant factors (e.g., MCP-1).29 Most of these factors are involved in the pathogenesis of liver fibrosis.4 Here, we show that HuR silencing in a cholestactic liver injury model (i.e., BDL) reduces the expression of several of these genes, leading to decreased liver damage, oxidative stress, inflammation, macrophage infiltration, and liver fibrosis development.

TGF-β is another major mediator of liver fibrogenesis.25 HuR silencing in the CFSC-8B cell line markedly reduced

up-regulation of col1a1, α-SMA, and TGF-β mRNA after TGF-β treatment (Fig. 8A). RIP-qPCR analysis showed that α-SMA and TGF-β, but not col1a1, were bound to HuR in TGF-β-stimulated cells (Fig. 8A). In HSCs, TGF-β also plays a major role in inhibiting proliferation in HSCs.26 TGF-β treatment decreased levels of the cell-cycle activators, cyclin D1 and B1, while increasing levels of the cell-cycle inhibitor, p21 (Supporting Fig. 7A,B). HuR knockdown abrogated the antiproliferative effects of TGF-β in primary HSCs from BDL mice (Supporting Fig. 7C) and in the CFSC-8B cell line (Fig. 8B). This

antiproliferative effect of TGF-β was likely the result of reduced p21 levels (Fig. 8C). RIP-qPCR showed that TGF-β treatment induced an http://www.selleckchem.com/products/abc294640.html increased binding of HuR to p21 while reducing the interaction of cyclin D1 and B1 mRNA with HuR (Fig. 8C). TGF-β treatment did not regulate HuR at mRNA and protein levels, unlike PDGF (Supporting Fig. 7D,E). However, TGF-β induced CP-868596 manufacturer increased cytoplasmic localization of HuR, both in primary HSCs (Supporting Fig. 3G) and in the CFSC-8B cell line (Fig. 8D and Supporting Fig. 7F). This translocation is unlikely to be mediated by ERK, AKT, or LKB1, because TGF-β did not activate any of these kinases (Fig. 8E). However, TGF-β activated p38 MAPK (Fig. 8E), and inhibition of this pathway prevented TGF-β-induced HuR translocation (Fig. 8F). TGF-β did not affect phosphorylation at any of the eight residues that we previously tested for PDGF-induced translocation (data not shown), suggesting that TGF-β and PDGF mediate HuR translocation by different post-translational modifications. In summary, we found that the profibrogenic

and antiproliferative actions of TGF-β could be controlled by HuR-mediated regulation of critical genes. Liver fibrosis and cirrhosis result from the majority of chronic liver insults and represent a difficult clinical Branched chain aminotransferase challenge. Recent studies have shown that HuR regulates angiotensin II–induced kidney fibrosis27 and ventricular remodeling after myocardial infarction.28 However, HuR functions during liver fibrosis development are unknown. Several studies have shown that HuR regulates the expression of several mRNAs encoding proinflammatory cytokines (e.g., TNF-α, IL-6, TGF-β, and interferon-gamma), proinflammatory mediators (e.g., iNOS), and chemoattractant factors (e.g., MCP-1).29 Most of these factors are involved in the pathogenesis of liver fibrosis.4 Here, we show that HuR silencing in a cholestactic liver injury model (i.e., BDL) reduces the expression of several of these genes, leading to decreased liver damage, oxidative stress, inflammation, macrophage infiltration, and liver fibrosis development.

TGF-β is another major mediator of liver fibrogenesis.25 HuR silencing in the CFSC-8B cell line markedly reduced

up-regulation of col1a1, α-SMA, and TGF-β mRNA after TGF-β treatment (Fig. 8A). RIP-qPCR analysis showed that α-SMA and TGF-β, but not col1a1, were bound to HuR in TGF-β-stimulated cells (Fig. 8A). In HSCs, TGF-β also plays a major role in inhibiting proliferation in HSCs.26 TGF-β treatment decreased levels of the cell-cycle activators, cyclin D1 and B1, while increasing levels of the cell-cycle inhibitor, p21 (Supporting Fig. 7A,B). HuR knockdown abrogated the antiproliferative effects of TGF-β in primary HSCs from BDL mice (Supporting Fig. 7C) and in the CFSC-8B cell line (Fig. 8B). This

antiproliferative effect of TGF-β was likely the result of reduced p21 levels (Fig. 8C). RIP-qPCR showed that TGF-β treatment induced an DMXAA in vivo increased binding of HuR to p21 while reducing the interaction of cyclin D1 and B1 mRNA with HuR (Fig. 8C). TGF-β treatment did not regulate HuR at mRNA and protein levels, unlike PDGF (Supporting Fig. 7D,E). However, TGF-β induced LY2157299 increased cytoplasmic localization of HuR, both in primary HSCs (Supporting Fig. 3G) and in the CFSC-8B cell line (Fig. 8D and Supporting Fig. 7F). This translocation is unlikely to be mediated by ERK, AKT, or LKB1, because TGF-β did not activate any of these kinases (Fig. 8E). However, TGF-β activated p38 MAPK (Fig. 8E), and inhibition of this pathway prevented TGF-β-induced HuR translocation (Fig. 8F). TGF-β did not affect phosphorylation at any of the eight residues that we previously tested for PDGF-induced translocation (data not shown), suggesting that TGF-β and PDGF mediate HuR translocation by different post-translational modifications. In summary, we found that the profibrogenic

and antiproliferative actions of TGF-β could be controlled by HuR-mediated regulation of critical genes. Liver fibrosis and cirrhosis result from the majority of chronic liver insults and represent a difficult clinical Mannose-binding protein-associated serine protease challenge. Recent studies have shown that HuR regulates angiotensin II–induced kidney fibrosis27 and ventricular remodeling after myocardial infarction.28 However, HuR functions during liver fibrosis development are unknown. Several studies have shown that HuR regulates the expression of several mRNAs encoding proinflammatory cytokines (e.g., TNF-α, IL-6, TGF-β, and interferon-gamma), proinflammatory mediators (e.g., iNOS), and chemoattractant factors (e.g., MCP-1).29 Most of these factors are involved in the pathogenesis of liver fibrosis.4 Here, we show that HuR silencing in a cholestactic liver injury model (i.e., BDL) reduces the expression of several of these genes, leading to decreased liver damage, oxidative stress, inflammation, macrophage infiltration, and liver fibrosis development.

By asking whether caffeine consumption patterns had changed in the Cell Cycle inhibitor past 6 months or 5 years, an attempt was made to discern whether patients with more advanced fibrosis were decreasing

their caffeine intake. Most patients did not report a change in caffeine consumption patterns over time, but this is clearly an imperfect measure of this trend. Importantly, however, of patients reporting a change in intake over the past 5 years, there were similar numbers with and without advanced fibrosis, suggesting that worsening liver disease was not the impetus to alter consumption of caffeine. Other factors that may affect caffeine consumption such as socioeconomic status, education level, and recreational drug use, were also not considered in this analysis. A useful instrument for a comprehensive evaluation of caffeine consumption was developed, which proved easy to use and highly reproducible. Caffeine consumption was associated with a lower risk of advanced liver fibrosis, particularly in patients with HCV infection;

however, the data suggest that a beneficial effect requires caffeine consumption above a threshold of approximately 2 coffee-cup equivalents per day. The effect seemed to be most pronounced with caffeinated coffee as opposed to other caffeine-containing products. With accumulating data on the beneficial role of coffee and Selleck AZD1208 caffeine in liver disease, as well as the supporting in vitro data, it may now be time to consider Tobramycin a prospective study of coffee or caffeine on hepatic fibrogenesis. Additional Supporting Information may be found in the online version of this article. “
“In this study, we analyzed the rates and patterns of recurrences in hepatocellular carcinoma

(HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE) or radiofrequency ablation (RFA), and also examined the differences of recurrence patterns between TACE-treated and RFA-treated groups. We followed 309 consecutive HCC patients who achieved CR following TACE (n = 220) or RFA (n = 89) for a median of 68 months. Recurrence patterns were classified as local recurrence and secondary tumor according to location of recurrence (≤2 cm and >2 cm from primary tumor). Recurred HCC had been found in 231 out of 309 patients (75%) with CR by TACE or RFA; 112 local recurrences (48%), 100 secondary tumor (43%) and 19 both (9%). The cumulative recurrence rates at 1, 3 and 5 years were 22%, 64% and 79%, respectively.

8 In addition to the ability of HCV to trigger the TLR3 pathway,9, 10 the increased number of Th17 cells appears to be associated with the severity of liver inflammation in chronic HCV patients and treatment of infected patients with pegylated buy RGFP966 interferon (IFN)-α and ribavirin reduced the level of Th17-related cytokines.11 As one of the crucial factors for Th17 differentiation, thymic stromal lymphopoietin (TSLP), a member of the common γ-chain cytokine, is capable of activating (conditioning) DCs, thereby stimulating naïve T cells to differentiate into Th2 cells.12 In addition, DCs treated with both TSLP and poly (I:C) activate naïve T cells and

differentiate into Th2 and Th17 cells.8, 13 Thus, TSLP-activated DCs, which are known to be strong inducers of Th2 responses, can simultaneously induce Th17 cells under certain pathological conditions. In this report MK-1775 solubility dmso we demonstrate that the infection of hepatic cells in vitro by HCV triggers robust TSLP production and this HCV-induced production of TSLP is regulated in an nuclear factor kappa B (NFκB)-dependent manner. TSLP secreted by HCV-infected cells activates and conditions human

monocyte-derived DCs to enhance the production of Th17 differentiating cytokines, TGF-β, IL-6, and IL-21 by the DCs. Moreover, the addition of TSLP neutralizing antibody to the coculture of monocytes/DCs with HCV-infected hepatocytes blocks the production of these cytokines. Consistent with these data, we find that the hepatocyte-derived TSLP is readily detected in liver biopsies from chronic HCV patients. Our studies suggest a novel role for the hepatocyte-derived TSLP in the generation of CD4+ Th17 effector T cells through its ability to condition DCs to drive CD4+ Th17 differentiation. The potential implications of these findings in the development of HCV-induced chronic progressive liver disease are discussed. DC, dendritic

cell; HCV, hepatitis C virus; TSLP, thymic stromal lymphopoietin. Human L-gulonolactone oxidase hepatoma cell lines, Huh 7.5.1, were maintained in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 μg/mL). THP-1 cells purchased from the American Tissue Culture Collection (ATCC) were cultured in RPMI 1640 and supplements as recommended by ATCC. Liver biopsies and peripheral blood samples from chronic HCV or control patients were obtained from Dr. Hugo Rosen (University of Colorado). Blood samples were also obtained from the Virginia Blood Services. All information of age, gender, and HCV genotype were previously described.14, 15 For infection of cells with secreted HCV, Huh 7.5.1 permissive cells were seeded at 3 × 106 cells in a T75 plate for 24 hours. Cells were infected with 4 × 104 FFU (multiplicity of infection [MOI] of 0.01) of JFH-1 producing cell supernatant and cultured for 10 days in DMEM-10% FCS media.