pylori infection When comparing H pylori-infected children to a

pylori infection. When comparing H. pylori-infected children to adults, a clear pattern emerged whereby the children had a weaker Palbociclib chemical structure Th1 response. Although the density of H. pylori organisms was the same in children as compared to adults, the mean gastric concentration of IL-1 and TNF was significantly

higher in children. However, IL-2, IL-12, and IFN were significantly lower in children. In addition, the Th1 cytokines were noted to increase to adult levels by 18 years of age. As we continue to study and evaluate various vaccine strategies, a number of laboratories continue to focus on the mechanisms of protection following successful immunization. A study published in 2000 by Shirai et al. [47] suggested that salivary antibodies are a critical factor in successfully preventing H. pylori infection by vaccination. Ng et al. followed up and tried to confirm this observation by determining whether immune mediated Selleck Cilomilast changes and/or mucin production were key factors in protection following immunization [5, 48]. Although they were able to confirm increased levels of salivary IgA as a result of immunizations, there was no increase

in mucin production or cytokine levels. Based on this study, the protection mechanism against H. pylori following immunization does not appear to be mediated by the cytokines within the salivary glands. There is much evidence confirming that chronic H. pylori infection results in the production of T-regulatory cells which play a role in its chronicity. Winter et al. [49] also recently demonstrated that the VacA and γ-glutamyl transferase found in membrane vesicles may also inhibit T cells from clearing this infection. The final study regarding the protection mechanism following H. pylori immunization contributes to a collection of reports demonstrating that promoting either Th1 or Th17 immunity is sufficient to protect mice from H. pylori. To the extent that the host

response to H. pylori infection is generally limited due to the induction of regulatory T cells, there is now considerable evidence that the key to inducing protection is to pre-empt or override regulatory T-cell activity by promoting Th1 and/or Th17 mediated immunity. Indeed, Ding et al. [50] demonstrated that it was possible to induce sterilizing immunity in infected mice through cytokine therapy with IL-12, even in the absence of immunization. medchemexpress A previous study by Velin et al. [51] achieved a reduction in bacterial load using a short-term IL-17 therapy. These findings may be particularly relevant in the continuing efforts to improve an H. pylori vaccine for use in humans. While the success achieved in murine models has not translated well in clinical trials, the results of Ding et al. indicate that a significant improvement may be achieved by the addition of cytokine adjuvants, or the development of pharmacologic agents able to specifically induce Th1 or Th17 cells in the absence of toxicity. H.

pylori infection When comparing H pylori-infected children to a

pylori infection. When comparing H. pylori-infected children to adults, a clear pattern emerged whereby the children had a weaker see more Th1 response. Although the density of H. pylori organisms was the same in children as compared to adults, the mean gastric concentration of IL-1 and TNF was significantly

higher in children. However, IL-2, IL-12, and IFN were significantly lower in children. In addition, the Th1 cytokines were noted to increase to adult levels by 18 years of age. As we continue to study and evaluate various vaccine strategies, a number of laboratories continue to focus on the mechanisms of protection following successful immunization. A study published in 2000 by Shirai et al. [47] suggested that salivary antibodies are a critical factor in successfully preventing H. pylori infection by vaccination. Ng et al. followed up and tried to confirm this observation by determining whether immune mediated Pifithrin �� changes and/or mucin production were key factors in protection following immunization [5, 48]. Although they were able to confirm increased levels of salivary IgA as a result of immunizations, there was no increase

in mucin production or cytokine levels. Based on this study, the protection mechanism against H. pylori following immunization does not appear to be mediated by the cytokines within the salivary glands. There is much evidence confirming that chronic H. pylori infection results in the production of T-regulatory cells which play a role in its chronicity. Winter et al. [49] also recently demonstrated that the VacA and γ-glutamyl transferase found in membrane vesicles may also inhibit T cells from clearing this infection. The final study regarding the protection mechanism following H. pylori immunization contributes to a collection of reports demonstrating that promoting either Th1 or Th17 immunity is sufficient to protect mice from H. pylori. To the extent that the host

response to H. pylori infection is generally limited due to the induction of regulatory T cells, there is now considerable evidence that the key to inducing protection is to pre-empt or override regulatory T-cell activity by promoting Th1 and/or Th17 mediated immunity. Indeed, Ding et al. [50] demonstrated that it was possible to induce sterilizing immunity in infected mice through cytokine therapy with IL-12, even in the absence of immunization. MCE A previous study by Velin et al. [51] achieved a reduction in bacterial load using a short-term IL-17 therapy. These findings may be particularly relevant in the continuing efforts to improve an H. pylori vaccine for use in humans. While the success achieved in murine models has not translated well in clinical trials, the results of Ding et al. indicate that a significant improvement may be achieved by the addition of cytokine adjuvants, or the development of pharmacologic agents able to specifically induce Th1 or Th17 cells in the absence of toxicity. H.

pylori infection When comparing H pylori-infected children to a

pylori infection. When comparing H. pylori-infected children to adults, a clear pattern emerged whereby the children had a weaker ITF2357 research buy Th1 response. Although the density of H. pylori organisms was the same in children as compared to adults, the mean gastric concentration of IL-1 and TNF was significantly

higher in children. However, IL-2, IL-12, and IFN were significantly lower in children. In addition, the Th1 cytokines were noted to increase to adult levels by 18 years of age. As we continue to study and evaluate various vaccine strategies, a number of laboratories continue to focus on the mechanisms of protection following successful immunization. A study published in 2000 by Shirai et al. [47] suggested that salivary antibodies are a critical factor in successfully preventing H. pylori infection by vaccination. Ng et al. followed up and tried to confirm this observation by determining whether immune mediated Gefitinib research buy changes and/or mucin production were key factors in protection following immunization [5, 48]. Although they were able to confirm increased levels of salivary IgA as a result of immunizations, there was no increase

in mucin production or cytokine levels. Based on this study, the protection mechanism against H. pylori following immunization does not appear to be mediated by the cytokines within the salivary glands. There is much evidence confirming that chronic H. pylori infection results in the production of T-regulatory cells which play a role in its chronicity. Winter et al. [49] also recently demonstrated that the VacA and γ-glutamyl transferase found in membrane vesicles may also inhibit T cells from clearing this infection. The final study regarding the protection mechanism following H. pylori immunization contributes to a collection of reports demonstrating that promoting either Th1 or Th17 immunity is sufficient to protect mice from H. pylori. To the extent that the host

response to H. pylori infection is generally limited due to the induction of regulatory T cells, there is now considerable evidence that the key to inducing protection is to pre-empt or override regulatory T-cell activity by promoting Th1 and/or Th17 mediated immunity. Indeed, Ding et al. [50] demonstrated that it was possible to induce sterilizing immunity in infected mice through cytokine therapy with IL-12, even in the absence of immunization. 上海皓元医药股份有限公司 A previous study by Velin et al. [51] achieved a reduction in bacterial load using a short-term IL-17 therapy. These findings may be particularly relevant in the continuing efforts to improve an H. pylori vaccine for use in humans. While the success achieved in murine models has not translated well in clinical trials, the results of Ding et al. indicate that a significant improvement may be achieved by the addition of cytokine adjuvants, or the development of pharmacologic agents able to specifically induce Th1 or Th17 cells in the absence of toxicity. H.

1 The potential of human hepatic stem cells (hHpSCs) and other st

1 The potential of human hepatic stem cells (hHpSCs) and other stem/progenitors for pharmaceutical research, cell-based therapies, and tissue engineering relies on being able to isolate them, propagate them in culture and differentiate them to a functional mature cell fate(s).2 Current methods for differentiation of stem cells

involve subjecting cells to a mix of soluble signals and/or extracellular matrix components, and the stem cells must be treated with multiple sets of such signals over weeks of time. The Selleckchem Autophagy inhibitor adult fate achieved is typical of only partially differentiated cells with over- or underexpression of specific adult genes.3 Here we demonstrate strategies for rapidly differentiating stem cells using matrix scaffolds that elicit more efficient and reproducible responses. Extracellular matrix is an extraordinarily complex mixture of molecules that are highly regulated, secreted by, and adjacent to cells on one or more of their surfaces, and long understood to be critical for determining check details the morphology,

growth, and differentiation of attached cells.4, 5 Tissue-specific gene expression in cultured cells is improved by culturing the cells on or embedded in matrix extracts or purified matrix components.6, 7 However, individual matrix components, alone or in combination, are unable to recapitulate a tissue’s complex matrix chemistry and architecture. This is related to the fact that the matrix components are in patterns associated with natural tissue zones and with histological structures such as blood vessels. This complexity of the tissue matrix is more readily achieved by matrix extracts of decellularized

tissue.8-10 Matrix extracts 上海皓元医药股份有限公司 found useful for ex vivo maintenance of cells include amniotic membrane extracts11; Matrigel, an urea extract of a murine embryonal carcinoma12; extracellular matrix (ECM), a detergent- or NaOH-extract of monolayer cell cultures13,14; and biomatrices, an extract of homogenized tissues.10, 15 More recently, decellularized tissues, prepared by collagenase digestion of a tissue16 or by delipidation followed by distilled water washes,8 have been used to mimic the matrix environment in vivo.17 Even though these protocols result in major losses of some matrix components, the decellularized scaffolds from different tissues or organs, such as small intestinal submucosa (SIS), bladder submucosa matrix (BSM),17, 18 vascular tissue,19 heart,20 airway,21 and liver22 have been used successfully in both preclinical and clinical applications.23 Here we describe a strategy, focused on collagen chemistry, that is ideal for preparing substrata of tissue extracts comprised of tissue-specific matrix components and factors bound to the matrix.

Patients with LC should undergo regular HCC surveillance even dur

Patients with LC should undergo regular HCC surveillance even during NAs therapy. Disclosures: Namiki Izumi – Speaking and Teaching: MSD Co., Chugai Co., Daiichi Sankyo Co., Bayer Co., Bristol Meyers Co. The following people have nothing to disclose: Etsuro Orito, Chitomi Hasebe, Masayuki Kurosaki, Atsunori Kusakabe, Yukio Osaki Background and Aims: Increased risk of renal proximal tubular injury resulting in decreased urinary phosphate reabsorption

and osteoporosis has been reported in HIV patients treated with tenofovir (TDF). Goals of this study were to evaluate the prevalence of abnormal renal phosphate wasting and abnormal bone mineral density (BMD) in a cohort of chronic hepatitis B (CHB) patients LEE011 mw taking TDF compared to CHB patients treated with entecavir (ETV) and untreated CHB patients. Patients and Methods: Cross-sectional study of 146 consecutive Asian-American CHB patients who were treatment naïve or treated with either TDF or ETV. Assignment of anti-viral agent was at the discretion of the physician. Testing included fasting blood and urinary levels of phosphate and creatinine to assess proximal tubular handling of phosphate by measuring maximal rate of tubular reabsorption

of phosphate (TmPO4) over glomerular filtration rate (GFR) (TmPO4/GFR). Abnormal TmPO4/GFR) was defined as < 2.8-4.4 mg/dL. BMD of the lumbar spine (from L1-L4) and hip was measured using dual X-ray absorptiometry (DEXA). Results: TmPO4/GFR was similar among

CHB patients treated with TDF (n=42) click here compared to untreated patients (n=60) and patients taking ETV (n=44). However, among patients treated with > 1 8 months of TDF or ETV, the prevalence of abnormal TmPO4/GFR was higher among patients treated with TDF 上海皓元医药股份有限公司 compared to ETV patients (48.5% (16/33) vs. 12.5% (3/24), p=0.005). Overall prevalence of osteoporosis (T score < -2.5) in this cohort of CHB patients was 14%, with no significant difference between the 3 groups. Patients with osteoporosis were older, had lower BMIs and higher serum alkaline phosphatase levels. There was no association with treatment or type of treatment and the presence of osteoporosis. Renal phosphate handling did not correlate with osteoporosis in this CHB cohort. The proportion of patients who had suffered fractures was uniformly low (< 5%) in all three groups. Conclusions: CHB patients treated > 1 8 months of TDF experienced an increased risk of proximal tubular dysfunction assessed by TmPO4/GFR. No clinical effects of abnormal TmPO4/GFR were seen. TDF did not increase the risk of osteoporosis or impaired creatinine clearance. Larger, preferably long term longitudinal studies are needed to confirm these findings. Phosphate Handling, Renal Function and Osteoporosis By Treatment Group Parameter Total N=146 No Treatment N=60 ETV N=44 TDF N=42 p value Phosphate threshold for renal tubular resorption Mean±SD % (n)<2.8 mg/dL 3.0±0.5 32% (46) 3.0+0.

Shen Hou and Qirui Liu for technical support Additional Supporti

Shen Hou and Qirui Liu for technical support. Additional Supporting Information may be found in the online version of this article. “
“The incidence of acute pancreatitis per 100 000 of population ranges from 5 to 80. Patients suffering from hemorrhagic-necrotizing pancreatitis die in 10–24% of cases. 80%

of all cases of acute pancreatitis are etiologically linked to gallstone disease immoderate alcohol consumption. As of today no specific causal treatment Autophagy pathway inhibitors for acute pancreatitis exists. Elevated C-reactive protein levels above 130 mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis or other infectious complications. However, as premature intracellular protease activation is known to be the primary event in acute pancreatitis. Severe acute pancreatitis is characterized by an early inflammatory Fostamatinib datasheet immune response syndrome (SIRS) and a subsequent compensatory anti-inflammatory response syndrome (CARS) contributing to severity as much as protease activation does. CARS suppresses the immune system and facilitates nosocomial infections including infected pancreatic necrosis, one of the most feared complications

of the disease. A number of attempts have been made to suppress the early systemic inflammatory response but even if these mechanisms have been found to be beneficial in

animal models they failed in daily clinical practice. “
“The identification and surveillance of patients with liver dysfunctions and the discovering of new disease biomarkers are needed in the clinical practice. The aim of this study was to investigate on Survivin–immunoglobulin (Ig)M immune complex (IC) as a potential biomarker of chronic liver diseases. Serum levels of Survivin–IgM were measured using an enzyme-linked immunoassay that had been standardized and validated in our laboratory in 262 individuals, including healthy subjects and patients with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Survivin–IgM IC was lower in healthy subjects (median, 上海皓元医药股份有限公司 99.39 AU/mL) than in patients with chronic viral hepatitis (median, 148.03 AU/mL; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P < 0.001). Among patients with cirrhosis, those with hepatitis C virus (HCV) infection showed the highest level of Survivin–IgM IC (median, 633.71 AU/mL; P < 0.001). The receiver–operator curve analysis revealed that Survivin–IgM accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis (area under the curve [AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A multivariate logistic regression model, including Survivin–IgM IC, aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT) ratio increased the prediction accuracy for the identification of the cirrhotic HCV patients (AUC, 0.818; sensitivity, 87.2%; specificity, 65.9%).

Shen Hou and Qirui Liu for technical support Additional Supporti

Shen Hou and Qirui Liu for technical support. Additional Supporting Information may be found in the online version of this article. “
“The incidence of acute pancreatitis per 100 000 of population ranges from 5 to 80. Patients suffering from hemorrhagic-necrotizing pancreatitis die in 10–24% of cases. 80%

of all cases of acute pancreatitis are etiologically linked to gallstone disease immoderate alcohol consumption. As of today no specific causal treatment Lumacaftor datasheet for acute pancreatitis exists. Elevated C-reactive protein levels above 130 mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis or other infectious complications. However, as premature intracellular protease activation is known to be the primary event in acute pancreatitis. Severe acute pancreatitis is characterized by an early inflammatory http://www.selleckchem.com/products/Nutlin-3.html immune response syndrome (SIRS) and a subsequent compensatory anti-inflammatory response syndrome (CARS) contributing to severity as much as protease activation does. CARS suppresses the immune system and facilitates nosocomial infections including infected pancreatic necrosis, one of the most feared complications

of the disease. A number of attempts have been made to suppress the early systemic inflammatory response but even if these mechanisms have been found to be beneficial in

animal models they failed in daily clinical practice. “
“The identification and surveillance of patients with liver dysfunctions and the discovering of new disease biomarkers are needed in the clinical practice. The aim of this study was to investigate on Survivin–immunoglobulin (Ig)M immune complex (IC) as a potential biomarker of chronic liver diseases. Serum levels of Survivin–IgM were measured using an enzyme-linked immunoassay that had been standardized and validated in our laboratory in 262 individuals, including healthy subjects and patients with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Survivin–IgM IC was lower in healthy subjects (median, 上海皓元医药股份有限公司 99.39 AU/mL) than in patients with chronic viral hepatitis (median, 148.03 AU/mL; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P < 0.001). Among patients with cirrhosis, those with hepatitis C virus (HCV) infection showed the highest level of Survivin–IgM IC (median, 633.71 AU/mL; P < 0.001). The receiver–operator curve analysis revealed that Survivin–IgM accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis (area under the curve [AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A multivariate logistic regression model, including Survivin–IgM IC, aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT) ratio increased the prediction accuracy for the identification of the cirrhotic HCV patients (AUC, 0.818; sensitivity, 87.2%; specificity, 65.9%).

Taken together, our data suggest NKT cells play a critical role i

Taken together, our data suggest NKT cells play a critical role in the development of early alcoholic

liver injury, neutrophil recruitment, www.selleckchem.com/products/AZD0530.html and inflammation. Future studies will be aimed at elucidating the mechanism(s) by which ethanol activates NKT cells and further investigating how activated NKT cells modify the critical inflammatory pathways involved in progression of ALD. Disclosures: The following people have nothing to disclose: Stephanie Mathews, Dechun Feng, Bin Gao Background: A PNPLA3 gene polymorphism (rs738409) is associated with liver fat content and histological severity in nonalcoholic fatty liver disease and with alcoholic cirrhosis. However the relationship between PNPLA3 genotype and acute alcoholic hepatitis (AAH), a distinct form of severe alcoholic liver disease, is unknown. The goal of this study was to determine whether rs738409 is associated with AAH and with differences in disease severity. Methods: We prospectively enrolled 46 patients admitted with severe AAH [Maddrey Discriminant Function (DF) >32]. As controls, we used 204 patients with history of heavy alcohol use (>8 and 15 drinks per week for females and males, respectively)

but no known liver disease enrolled in the Dactolisib in vivo North American Pancreatitis Study (NAPS2). Clinical and biochemical measures were recorded. Median values were reported and nonparametric statistical tests utilized. PNPLA3 genotype in cases and controls was determined by real-time PCR. We compared allele and genotype frequencies between patients with AAH and controls using Fisher’s exact and Chi-Square tests. We compared markers of disease severity using Kruskal-Wallis test. Results: The G allele was more frequent in patients with AAH compared with controls (0.32 vs 0.19; p< 0.01). Of the patients with AAH, 46% had CC genotype, 43% had CG genotype, and 11% had GG genotype, compared with controls,

of which 67% had CC genotype, 上海皓元医药股份有限公司 27% had CG genotype, and 5% had GG genotype (p =0.02). Since AAH patients were predominantly male and Caucasian, we stratified the analysis by race and gender. Amongst Caucasian patients, 47% of AAH patients had CC genotype, 42% had CG genotype and 11% had GG genotype compared with 66% CC, 29% CG, and 6% GG (p = 0.056). Male AAH patients (n=34) had genotype frequencies of CC 41%, CG 50%, GG 9% versus male controls (n=100) with frequencies of CC 67%, CG 25%, and GG 8% (p=0.02). Female AAH patients (n=11) had genotype frequencies of CC 64%, CG 18%, GG 18% compared with female controls (n=105) with CC 68%, CG 29%, GG 3% (p = 0.05). To determine whether PNPLA3 gene variants were associated with disease severity in AAH, we determined Model for Endstage Liver Disease (MELD) scores on the first day of admission. Patients with GG genotype had higher MELD scores (MELD 31 in GG genotype versus MELD 26 in CC genotype; p < 0.05).

Taken together, our data suggest NKT cells play a critical role i

Taken together, our data suggest NKT cells play a critical role in the development of early alcoholic

liver injury, neutrophil recruitment, click here and inflammation. Future studies will be aimed at elucidating the mechanism(s) by which ethanol activates NKT cells and further investigating how activated NKT cells modify the critical inflammatory pathways involved in progression of ALD. Disclosures: The following people have nothing to disclose: Stephanie Mathews, Dechun Feng, Bin Gao Background: A PNPLA3 gene polymorphism (rs738409) is associated with liver fat content and histological severity in nonalcoholic fatty liver disease and with alcoholic cirrhosis. However the relationship between PNPLA3 genotype and acute alcoholic hepatitis (AAH), a distinct form of severe alcoholic liver disease, is unknown. The goal of this study was to determine whether rs738409 is associated with AAH and with differences in disease severity. Methods: We prospectively enrolled 46 patients admitted with severe AAH [Maddrey Discriminant Function (DF) >32]. As controls, we used 204 patients with history of heavy alcohol use (>8 and 15 drinks per week for females and males, respectively)

but no known liver disease enrolled in the AZD9668 in vitro North American Pancreatitis Study (NAPS2). Clinical and biochemical measures were recorded. Median values were reported and nonparametric statistical tests utilized. PNPLA3 genotype in cases and controls was determined by real-time PCR. We compared allele and genotype frequencies between patients with AAH and controls using Fisher’s exact and Chi-Square tests. We compared markers of disease severity using Kruskal-Wallis test. Results: The G allele was more frequent in patients with AAH compared with controls (0.32 vs 0.19; p< 0.01). Of the patients with AAH, 46% had CC genotype, 43% had CG genotype, and 11% had GG genotype, compared with controls,

of which 67% had CC genotype, medchemexpress 27% had CG genotype, and 5% had GG genotype (p =0.02). Since AAH patients were predominantly male and Caucasian, we stratified the analysis by race and gender. Amongst Caucasian patients, 47% of AAH patients had CC genotype, 42% had CG genotype and 11% had GG genotype compared with 66% CC, 29% CG, and 6% GG (p = 0.056). Male AAH patients (n=34) had genotype frequencies of CC 41%, CG 50%, GG 9% versus male controls (n=100) with frequencies of CC 67%, CG 25%, and GG 8% (p=0.02). Female AAH patients (n=11) had genotype frequencies of CC 64%, CG 18%, GG 18% compared with female controls (n=105) with CC 68%, CG 29%, GG 3% (p = 0.05). To determine whether PNPLA3 gene variants were associated with disease severity in AAH, we determined Model for Endstage Liver Disease (MELD) scores on the first day of admission. Patients with GG genotype had higher MELD scores (MELD 31 in GG genotype versus MELD 26 in CC genotype; p < 0.05).

Median survival was 26 months in the TIPS group (n=65) vs 27 mon

Median survival was 26 months in the TIPS group (n=65) vs. 27 months without TIPS (n=65), p=1.00. Median follow up was 12 months. Rate of infection did not differ between the 2 groups. Main complications of TIPS (recurrent encephalopathy 34%, stent dysfunction 24.5%, strangulated umbilical hernia 9%, congestive heart failure

7.5%) did not affect patient survival. Conclusion : in this series, TIPS with covered stents appears to improve the natural history of Child-Pugh B cirrhosis with recurrent decompensation. Conversely, decreasing portosystemic pressure gradient does not alter the progression of Child-Pugh C cirrhosis with prolonged decompensation. Earlier implementation of a tips should be discussed for some child-pugh B patients with recurrent ascites or gastrointestinal bleeding. Disclosures: Xavier Adhoute – Speaking and Omipalisib molecular weight Teaching: bayer Marc Bourlière – Advisory Committees or Review Panels: Schering-Plough, Bohringer inghelmein, Schering-Plough, Bohringer inghelmein; Board Membership: Bristol-Myers Squibb, Gilead, Idenix; Consulting: Roche, Novartis, Tibotec, Abott, glaxo smith kline, Merck, Bristol-Myers Squibb, Novartis, Tibotec, Abott, glaxo smith kline; Speaking and Teaching: Gilead, Roche, Merck, Bristol-Myers Squibb IWR-1 ic50 The following people have nothing to disclose: Paul

Castellani, Guillaume Penaranda, Olivier Monnet, Herve Perrier, Bernard L. Pol, Cyril Muller, Arthur Laquiere, Valerie Oules, Patrick Beaurain, Christian Boustiere, Olivier Bayle “
“Interleukin-22 (IL-22) plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces by binding to the receptors IL-22R1, which is generally thought to be expressed exclusively in epithelial cells, and IL-10R2. Our laboratory previously demonstrated MCE that IL-22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL-22R1 and IL-10R2. Recently, we have identified high expression levels of IL-22R1 and IL-10R2 in

liver progenitor cells and hepatic stellate cells (HSCs). Overexpression of IL-22 in vivo or treatment with IL-22 in vitro promotes proliferation of liver progenitor cells via a signal transducer and activator of transcription 3 (STAT3)-dependent mechanism. IL-22 treatment also prevents HSC apoptosis in vitro and in vivo. Surprisingly, overexpression of IL-22, via either gene targeting or exogenous administration of adenovirus expressing IL-22, reduces liver fibrosis and accelerates the resolution of liver fibrosis during recovery. The anti-fibrotic effects of IL-22 are mediated via the activation of STAT3 in HSCs and subsequent induction of suppressor of cytokine signaling 3, which induces HSC senescence. Taken together, the hepatoprotective, mitogenic, and anti-fibrotic effects of IL-22 are beneficial in ameliorating alcoholic liver injury.