Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system.

Abstract:

BACKGROUND & AIMS:ob/ob mice are used to study the mechanisms that regulate the progression from steatosis to nonalcoholic steatohepatitis. The livers of ob/ob mice are depleted of CD4-positive natural killer cells, components of the innate immune system that induce anti-inflammatory cytokines. Although this may explain the sensitivity of fatty livers to lipopolysaccharide, why such hepatic CD4-positive natural killer cell depletion occurs is uncertain. Because leptin regulates macrophages, our hypothesis is that leptin deficiency alters Kupffer cell production of cytokines that inhibit (e.g., interleukin [IL]-12) or enhance (e.g., IL-15) hepatic CD4-positive natural killer cell viability. METHODS:Kupffer cell cytokine production and the hepatic content of CD4-positive natural killer cells were compared in ob/ob and lean mice. ob/ob mice were then treated with IL-15 or leptin to determine whether either factor improved their immunologic abnormalities. RESULTS:Compared with control Kupffer cells, ob/ob Kupffer cells produced less IL-15 basally and more IL-12 after lipopolysaccharide stimulation. Treatment of ob/ob mice with IL-15 for 1 week normalizes their hepatic CD4-positive natural killer cell content. Leptin increases the hepatic expression of IL-15 in ob/ob mice and partially replenishes their hepatic CD4-positive natural killer cells. CONCLUSIONS:Leptin deficiency increases hepatic IL-12 and reduces hepatic IL-15 expression. The abnormal production of these Kupffer cell factors promotes hepatic CD4-positive natural killer cell depletion in ob/ob livers.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Li Z,Lin H,Yang S,Diehl AM

doi

10.1053/gast.2002.35997

keywords:

subject

Has Abstract

pub_date

2002-10-01 00:00:00

pages

1304-10

issue

4

eissn

0016-5085

issn

1528-0012

pii

S0016508502002330

journal_volume

123

pub_type

杂志文章
  • Cholinergic effects on gallbladder emptying in humans.

    abstract::The role of cholinergic mechanisms in the control of gallbladder emptying has not been defined. In this report a scintigraphic technique using 2,6-dimethylphenylcarbamoylmethyl iminodiacetic acid labeled with technetium 99m to visualize the gallbladder and its emptying and diethylenetriamine pentaacetic acid labeled w...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(85)90564-5

    authors: Fisher RS,Rock E,Malmud LS

    更新日期:1985-10-01 00:00:00

  • Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

    abstract:BACKGROUND & AIMS:Postprandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among patients with recurrent hypoglycemia. These patients also have increased postprandial levels of insulin and glucagon-like peptide 1 (GLP-1). We performed a clinical trial to determine the role of ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2013.11.044

    authors: Salehi M,Gastaldelli A,D'Alessio DA

    更新日期:2014-03-01 00:00:00

  • Zinc deficiency: a complication of Crohn's disease.

    abstract::Twenty-one of 52 patients with regional enteritis had low serum zinc concentrations on initial testing. Fourteen of 31 patients followed longitudinally had low serum zinc concentrations. Two patients are presented as case reports who developed acrodermatitis skin lesions that responded to zinc therapy. Hypogonadism, g...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: McClain C,Soutor C,Zieve L

    更新日期:1980-02-01 00:00:00

  • Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn's disease.

    abstract::Increased dietary ratios of ω6/ω3 polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease (CD), but epidemiologic data are limited. We investigated whether variants of genes that control polyunsaturated fatty acid metabolism (CYP4F3, FADS1, and FADS2), along with the dietary ratio of ω6...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2013.12.034

    authors: Costea I,Mack DR,Lemaitre RN,Israel D,Marcil V,Ahmad A,Amre DK

    更新日期:2014-04-01 00:00:00

  • Compositional and functional features of the gastrointestinal microbiome and their effects on human health.

    abstract::The human gastrointestinal tract contains distinct microbial communities that differ in composition and function based on their location, as well as age, sex, race/ethnicity, and diet of their host. We describe the bacterial taxa present in different locations of the GI tract, and their specific metabolic features. Th...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2014.01.052

    authors: Hollister EB,Gao C,Versalovic J

    更新日期:2014-05-01 00:00:00

  • Rotaviruses: from pathogenesis to vaccination.

    abstract::Rotaviruses cause life-threatening gastroenteritis in children worldwide; the enormous disease burden has focused efforts to develop vaccines and led to the discovery of novel mechanisms of gastrointestinal virus pathogenesis and host responses to infection. Two live-attenuated vaccines for gastroenteritis (Rotateq [M...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2009.02.076

    authors: Greenberg HB,Estes MK

    更新日期:2009-05-01 00:00:00

  • Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma.

    abstract:BACKGROUND & AIMS:Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds. METHODS:TP53 mutation...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2010.11.034

    authors: Woo HG,Wang XW,Budhu A,Kim YH,Kwon SM,Tang ZY,Sun Z,Harris CC,Thorgeirsson SS

    更新日期:2011-03-01 00:00:00

  • Molecular, genetic, and cellular bases for treating eosinophilic esophagitis.

    abstract::Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2015.02.002

    authors: Rothenberg ME

    更新日期:2015-05-01 00:00:00

  • Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells.

    abstract:BACKGROUND & AIMS:The mechanisms by which hepatitis C virus (HCV) induces liver fibrosis are unknown. Hepatocytes secrete HCV proteins, which may interact with hepatic stellate cells (HSCs). Our aims were to investigate whether HCV proteins induce fibrogenic effects on HSCs. METHODS & RESULTS:Human-activated HSCs expr...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2003.11.018

    authors: Bataller R,Paik YH,Lindquist JN,Lemasters JJ,Brenner DA

    更新日期:2004-02-01 00:00:00

  • Effect of bile acid synthesis rate on cholesterol secretion rate in the steady state.

    abstract::In order to discover the effect of bile acid synthesis on cholesterol secretion into the bile, 7 rhesus monkeys were studied at various stable interruptions of the enterohepatic circulation of bile acids. In 4 animals, 2.5 and 7.5% interruptions were compared; 2.5 and 15% interruptions were compared in 5 animals. Ther...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Strasberg SM,Petrunka CN,Ilson RG

    更新日期:1976-12-01 00:00:00

  • Treatment of acute pancreatitis. Comparison of animal and human studies.

    abstract::In this review, we compared the outcome of 25 studies of experimentally induced pancreatitis in animals with 13 studies of human acute pancreatitis in which the same therapeutic agents were used (aprotinin, glucagon, 5-fluorouracil, somatostatin, peritoneal lavage). Whereas 81% of the animal studies had a positive out...

    journal_title:Gastroenterology

    pub_type: 临床试验,杂志文章,评审

    doi:10.1016/0016-5085(87)90275-7

    authors: Steinberg WM,Schlesselman SE

    更新日期:1987-12-01 00:00:00

  • Bone marrow retaining colitogenic CD4+ T cells may be a pathogenic reservoir for chronic colitis.

    abstract:BACKGROUND & AIMS:Although bone marrow (BM) is known as a primary lymphoid organ, it also is known to harbor memory T cells, suggesting that this compartment is a preferential site for migration and/or selective retention of memory T cells. We here report the existence and the potential ability to induce colitis of the...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2006.10.035

    authors: Nemoto Y,Kanai T,Makita S,Okamoto R,Totsuka T,Takeda K,Watanabe M

    更新日期:2007-01-01 00:00:00

  • Detection of hepatitis B virus infection in hepatitis B surface antigen-negative hemodialysis patients by monoclonal radioimmunoassays.

    abstract::We studied 375 chronic hemodialysis patients for evidence of hepatitis B virus infection using first- and second-generation monoclonal radioimmunoassays. These assays employ high-affinity monoclonal antibodies produced against antigenic determinants that reside on hepatitis B surface antigen. Such assays have a lower ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(86)90187-3

    authors: Fujita YK,Kamata K,Kameda H,Isselbacher KJ,Wands JR

    更新日期:1986-12-01 00:00:00

  • An examination of liver offers to candidates on the liver transplant wait-list.

    abstract:BACKGROUND & AIMS:We aimed to characterize offers of organs to candidates awaiting liver transplantation (LT). METHODS:We analyzed data from the United Network for Organ Sharing registry on all US LT candidates with nonfulminant disease who were offered livers from February 1, 2005, to January 31, 2010, and ultimately...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2012.07.105

    authors: Lai JC,Feng S,Roberts JP

    更新日期:2012-11-01 00:00:00

  • The professional lives of women in gastroenterology: a Canadian comparison study with men.

    abstract::Women are underrepresented in gastroenterology. A questionnaire examined the training and career experiences of female members of the Canadian Association for Gastroenterology (CAG) and their male counterparts. A pretested questionnaire was mailed to the 50 female CAG and 100 age-matched male members. Descriptive anal...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.1997.v113.pm9247490

    authors: Heathcote J,Cauch-Dudek K,Rhyne D

    更新日期:1997-08-01 00:00:00

  • Increased production of retinoic acid by intestinal macrophages contributes to their inflammatory phenotype in patients with Crohn's disease.

    abstract:BACKGROUND & AIMS:Reduced generation of all-trans retinoic acid (RA) by CD103(+) intestinal dendritic cells (DCs) is linked to intestinal inflammation in mice. However, the role of RA in intestinal inflammation in humans is unclear. We investigated which antigen-presenting cells (APCs) produce RA in the human intestine...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2014.01.057

    authors: Sanders TJ,McCarthy NE,Giles EM,Davidson KL,Haltalli ML,Hazell S,Lindsay JO,Stagg AJ

    更新日期:2014-05-01 00:00:00

  • MLH1 germline epimutations as a factor in hereditary nonpolyposis colorectal cancer.

    abstract:BACKGROUND & AIMS:Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by heterozygous germline sequence mutations of DNA mismatch repair genes, most frequently MLH1 or MSH2. A novel molecular mechanism for HNPCC has recently been suggested by the finding of individuals with soma-wide monoallelic hypermethylatio...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2005.09.003

    authors: Hitchins M,Williams R,Cheong K,Halani N,Lin VA,Packham D,Ku S,Buckle A,Hawkins N,Burn J,Gallinger S,Goldblatt J,Kirk J,Tomlinson I,Scott R,Spigelman A,Suter C,Martin D,Suthers G,Ward R

    更新日期:2005-11-01 00:00:00

  • Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study.

    abstract:BACKGROUND & AIMS:Helicobacter pylori-negative idiopathic ulcers are increasingly recognized. The secular trend and long-term outcome of this condition are unknown. METHODS:We prospectively studied consecutive patients with bleeding gastroduodenal ulcers from January to December 2000. The incidence and etiology of ulc...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2005.03.026

    authors: Hung LC,Ching JY,Sung JJ,To KF,Hui AJ,Wong VW,Leong RW,Chan HL,Wu JC,Leung WK,Lee YT,Chung SC,Chan FK

    更新日期:2005-06-01 00:00:00

  • Diabetes increases the risk of acute hepatic failure.

    abstract:BACKGROUND & AIMS:It is unclear whether patients with diabetes are at an increased risk of developing acute liver failure (ALF). We performed a large cohort study to examine the occurrence of ALF by using the databases of the Department of Veterans Affairs. METHODS:We identified all patients with a hospital discharge ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2002.33650

    authors: El-Serag HB,Everhart JE

    更新日期:2002-06-01 00:00:00

  • Treatment of Zollinger-Ellison syndrome with exploratory laparotomy, proximal gastric vagotomy, and H2-receptor antagonists. A prospective study.

    abstract::Twenty-two patients with Zollinger-Ellison syndrome were managed by a combined medical and surgical approach. Patients were treated initially with cimetidine or ranitidine. A laparotomy was performed to remove easily resectable tumors and to carry out a proximal gastric vagotomy. Tumors were found in 9 patients (41%) ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(85)90337-3

    authors: Richardson CT,Peters MN,Feldman M,McClelland RN,Walsh JH,Cooper KA,Willeford G,Dickerman RM,Fordtran JS

    更新日期:1985-08-01 00:00:00

  • Colonoscopic polypectomy: silent perforation.

    abstract::The management of colon polyps has been completely revolutionized since the introduction of colonoscopic polypectomy. The reductions in patient time, cost, morbidity, and mortality are major advantages. Reported complications include primarily hemorrhage (1.7%) and frank clinical perforation (0.32%). This report descr...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Overholt BF,Hargrove RL,Farris RK,Wilson BM

    更新日期:1976-01-01 00:00:00

  • Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish.

    abstract:BACKGROUND & AIMS:Biliary epithelial cells (BECs) are considered to be a source of regenerating hepatocytes when hepatocyte proliferation is compromised. However, there is still controversy about the extent to which BECs can contribute to the regenerating hepatocyte population, and thereby to liver recovery. To investi...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2013.10.019

    authors: Choi TY,Ninov N,Stainier DY,Shin D

    更新日期:2014-03-01 00:00:00

  • Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.

    abstract:BACKGROUND & AIMS:Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS:We perf...

    journal_title:Gastroenterology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1053/j.gastro.2015.10.050

    authors: Carbonnel F,Colombel JF,Filippi J,Katsanos KH,Peyrin-Biroulet L,Allez M,Nachury M,Novacek G,Danese S,Abitbol V,Bossa F,Moreau J,Bommelaer G,Bourreille A,Fumery M,Roblin X,Reinisch W,Bouhnik Y,Brixi H,Seksik P,Mala

    更新日期:2016-02-01 00:00:00

  • Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma.

    abstract:BACKGROUND & AIMS:De novo lipogenesis is believed to be involved in oncogenesis. We investigated the role of aberrant lipid biosynthesis in the pathogenesis of human hepatocellular carcinoma (HCC). METHODS:We evaluated expression of enzymes that regulate lipogenesis in human normal liver tissues and HCC and surroundin...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2010.12.006

    authors: Calvisi DF,Wang C,Ho C,Ladu S,Lee SA,Mattu S,Destefanis G,Delogu S,Zimmermann A,Ericsson J,Brozzetti S,Staniscia T,Chen X,Dombrowski F,Evert M

    更新日期:2011-03-01 00:00:00

  • Markers of fibrogenesis and basement membrane formation in alcoholic liver disease. Relation to severity, presence of hepatitis, and alcohol intake.

    abstract::This study investigated the relationships of the serum markers of fibrogenesis and basement membrane formation to the clinical and morphological severity of alcoholic liver disease and to the degree of alcohol abuse. The concentrations of the aminoterminal propeptide of type III collagen, type IV collagen, and laminin...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(90)91098-q

    authors: Niemelä O,Risteli J,Blake JE,Risteli L,Compton KV,Orrego H

    更新日期:1990-06-01 00:00:00

  • Ultrasonic properties of gallstones. Effect of stone size and composition.

    abstract::In vivo and in vitro ultrasonic characteristics of gallstones were compared with stone size and composition with the aim of understanding the basis for these features. In vivo and in vitro ultrasonic features of the same stone were identical. Acoustic shadowing was not due to stone type, radiodensity, or calcium conte...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Good LI,Edell SL,Soloway RD,Trotman BW,Mulhern C,Arger PA

    更新日期:1979-08-01 00:00:00

  • The Intestinal Microenvironment and Functional Gastrointestinal Disorders.

    abstract::For decades, interactions between the enteric neuromuscular apparatus and the central nervous system have served as the primary focus of pathophysiological research in the functional gastrointestinal disorders. The accumulation of patient reports, as well as clinical observations, has belatedly led to an interest in t...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2016.02.028

    authors: Barbara G,Feinle-Bisset C,Ghoshal UC,Quigley EM,Santos J,Vanner S,Vergnolle N,Zoetendal EG

    更新日期:2016-02-18 00:00:00

  • Piezoelectric lithotripsy: stone disintegration and follow-up results in patients with symptomatic gallbladder stones.

    abstract::One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(90)91173-4

    authors: Ell C,Kerzel W,Schneider HT,Benninger J,Wirtz P,Domschke W,Hahn EG

    更新日期:1990-11-01 00:00:00

  • Reduced mortality rates following elective percutaneous liver biopsies.

    abstract:BACKGROUND & AIMS:Estimates of complication rates following elective percutaneous liver biopsy vary and might not accurately reflect current practice. We studied mortality and complication rates, by indication, in patients after they underwent liver biopsies. METHODS:We performed a study using hospital episode statist...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2010.06.015

    authors: West J,Card TR

    更新日期:2010-10-01 00:00:00

  • Colonic mucin composition in primates. Selective alterations associated with spontaneous colitis in the cotton-top tamarin.

    abstract::Heterogeneity of colonic mucin glycoprotein was examined in rectal mucosal biopsy specimens from a variety of primate species (Saguinus oedipus, n = 18; Macaca mulatta, n = 2; Macaca fascicularis, n = 2; Aotus trivirgatus, n = 2; Saimiri sciureus, n = 2; and Callithrix jacchus, n = 2). After initial separation of radi...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(85)80127-x

    authors: Podolsky DK,Madara JL,King N,Sehgal P,Moore R,Winter HS

    更新日期:1985-01-01 00:00:00