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Biomedical subjects

Tooru Shimosegawa

Publications and source records attributed to Tooru Shimosegawa.

At least 127 records · Page 7Linked to original sources
PubMed2002

Gene expression of interleukin-12 receptor beta2 chain and Th1 population of peripheral blood mononuclear cells in chronic hepatitis C.

Gene expression of interleukin 12-receptor beta2 chain mRNA in peripheral blood mononuclear cells (PBMCs) was examined in patients with chronic hepatitis C (n=7) and in healthy control subjects (n=6) by semi-quantitative RT-PCR. The level of interleukin 12-receptor beta2 chain mRNA was higher in patients with chronic hepatitis C than in healthy subjects (P=0.032). The level of interleukin 12-receptor beta2 chain mRNA had a weak correlation with the ratio of Th1 to Th2 populations (r=0.714, P=0.020). There was a tendency for the level of interleukin 12-receptor beta2 mRNA to increase both in chronic hepatitis C (P=0.109) and in healthy volunteers (P=0.144) after the incubation of PBMCs with interferon-alpha in vitro. During interferon-alpha administration to the patients with chronic hepatitis C, the level of interleukin 12-receptor beta2 chain mRNA in PBMCs was increased in all four cases. Although this is a preliminary study with a small sample size, our results suggest that the level of interleukin 12-receptor beta2 chain mRNA is higher than normal in patients with chronic hepatitis C and can be further enhanced by interferon therapy.

Journal Article↗
PubMed2002

Analysis of the entire nucleotide sequence of hepatitis B virus: characteristics of HBeAg-positive asymptomatic carriers, HBeAb positive asymptomatic carriers and patients with liver cirrhosis.

Entire nucleotide sequences of the HBV genome typical for various stages of HBV carriers are currently unknown. Comparison between conserved sequences in HBeAg-positive asymptomatic carriers (HBeAg ASCs) and mutations characteristic for HBeAb-positive asymptomatic carriers (HBeAb ASCs) are of clinical importance. In this study, we determined the entire nucleotide sequences of the HBV genome of patients infected with genotype C (HBeAg ASCs, 11 cases; HBeAb ASCs, seven cases; patients with liver cirrhosis (LC), five cases). Mutations in the entire nucleotide sequences were found more frequently in HBeAb ASCs than in HBeAg ASCs. In the precore/core (preC/C) region, amino acid mutations were more frequent in HBeAb ASCs (3.03%) than in HBeAg ASCs (0.00%) and patients with LC (0.69%). It was suggested that the mutations in the preC/C region had a close relationship with clinical status of HBV carriers. Mutations of leucine to isoleucine at a.a. 100 of the core region and of threonine to serine at a.a. 340 of the polymerase region were found frequently in HBeAb ASCs. In patients with LC, it was suggested that defective interfering particles (DI particles) play a role in the progression of stages. We conclude that attention should be given to mutations at a.a. 340 of the polymerase protein in addition to core protein.

Journal Article↗
PubMed2002

Up-regulation of CD11a (LFA-1) expression on peripheral CD4+ T cells in primary biliary cirrhosis.

Up-regulation of CD11a expression on CD4+ T lymphocytes is considered to be one of the mechanisms involved in the initiation of the Th-1-mediated immune response. In this study, peripheral blood mononuclear cells from patients with primary biliary cirrhosis (PBC) were evaluated for CD11a(high) CD2(low) T cells and populations of type 1 (Th-1) and type 2 (Th-2) helper T cells. CD11a(high) CD2(low) T cells were found in PBC (7/15) and in active rheumatoid arthritis (4/4), but not in chronic hepatitis C (0/5) or in healthy subjects (0/6). The population of Th-1 had a positive correlation with that of CD4+ CD11a(high) CD2+ cells in patients with PBC (P = 0.034). The serum levels of interferon-gamma also had a weak correlation with the population of CD4+ CD11a(high) CD2(low) cells (P = 0.050). There was no statistically significant correlation of Th-2 population (P = 0.295) or serum interleukin-4 level (P = 0.685) with the population of CD4+ CD11a(high) CD2(low) cells. These results suggest that CD4+ CD11a(high) cells play a role in Th-1-predominance and in the autoimmune process of PBC.

Arthritis, Rheumatoid↗
PubMed2002

Analysis of cell damage in Helicobacter pylori-associated gastritis.

Helicobacter pylori infection is currently considered to be a major cause of acute and chronic gastritis, and of gastric and duodenal ulcers. Superoxide dismutase (SOD) is well known for scavenging superoxide radicals such as reactive oxygen species (ROS), subsequently protecting cells from oxidative injury, and for maintaining tissue homeostasis. In this study, we therefore evaluated the level of SOD activity and protein expression, as well as various factors associated with oxidative injury, in H. pylori-positive (n = 46) and -negative (n = 28) gastric mucosa obtained from endoscopy, in order to elucidate the possible biological significance of SOD in these mucosa. Overall SOD activity was significantly higher in H. pylori-positive mucosa (15.5 +/- 7.0 U/mg protein) than in negative mucosa (9.2 +/- 10.6 U/mg protein), and decreased markedly following H. pylori eradication (8.2 +/- 4.2 U/mg protein). Enzyme-linked immunosorbent assay (ELISA) analysis of SOD revealed that the manganese SOD (Mn-SOD) level in H. pylori-positive mucosa (1166.7 +/- 435.2 ng/mg protein) was significantly higher than in control tissues (446.3 +/- 435.3 ng/mg protein) and in mucosa obtained following eradication therapy (431.9 +/- 189.9 ng/mg protein). The level of Mn-SOD protein showed a significant correlation with degree of inflammation in the gastric mucosa. Moreover, Mn-SOD immunolocalization patterns were well correlated with the activity and protein levels evaluated by ELISA. Factors presumably associated with oxidative injury in human gastric mucosa, including terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, Ki-67, 8-hydroxydeoxyguanosine and single-stranded DNA, were all significantly higher in H. pylori-positive gastric mucosa than in control tissue and in tissue following eradication. These results all suggest that Mn-SOD, but not cytoplasmic copper-zinc SOD, plays an important role as an anti-oxidant against ROS generated in H. pylori-infected gastric mucosa and, subsequently, in the maintenance of cell turnover in gastric mucosa.

DNA, Single-Stranded↗
PubMed2002

Localization of antigen-presenting cells in Helicobacter pylori-infected gastric mucosa.

Helicobacter pylori (HP) infection is known to induce the specific immune response in the gastric mucosa. The immune response is triggered by presentation of antigen peptides on the major histocompatibility assembly of the antigen-presenting cells (APC) with the assistance of costimulatory molecules such as B7-1 (CD80) and B7-2 (CD86). Their counter-receptors or ligands on T cells are CD28 or cytotoxic lymphocyte-associated molecule-4. The aim of the present study was to clarify the localization of APC and their relation with T cells in HP-infected human gastric mucosa. Our findings suggest that the macrophages in the lamina propria may mainly act as APC in the HP-infected gastric mucosa, and the triggered immune response might be involved in the mucosal immune response in the inflamed gastric mucosa to invasive antigens related to HP organisms.

Anti-Bacterial Agents↗
PubMed2002

Lack of common NOD2 variants in Japanese patients with Crohn's disease.

BACKGROUND & AIMS: Previous studies have linked Crohn's disease (CD) to the pericentromeric region of chromosome 16 (IBD1). Three independent studies of Western populations have recently shown that 3 variants of NOD2, a gene located at 16q12, are associated with susceptibility to CD. Here, we have evaluated the 3 NOD2 variants in Japanese patients to determine whether the gene is also associated with susceptibility to CD in a non-Western population. METHODS: Blood samples were obtained from 350 patients with CD, 272 patients with ulcerative colitis, and 292 healthy controls at 3 hospitals in Japan. DNA was sequenced in the region of the 3 NOD2 variants (C2104T in exon 4, G2722C in exon 8, and 3020insC in exon 11) by genomic polymerase chain reaction followed by direct sequencing. RESULTS: Among the subjects in our 3 study groups, including patients with CD, patients with ulcerative colitis, and healthy controls, none had common NOD2 variants that have been associated with CD in white patients. CONCLUSIONS: These results indicate that genetic variation, which may predispose some human populations to CD, may not be present in other populations and specifically that common variants in NOD2 found in white patients with CD are not associated with CD in the Japanese population.

Adult↗
PubMed2002

Myosin light chain kinase inhibitors can block invasion and adhesion of human pancreatic cancer cell lines.

INTRODUCTION: Invasion and metastasis of pancreatic cancer (PC) require cell motility and adhesion, which depend on the activity of cytoskeleton. A cytoskeletal component indispensable for these processes is myosin II, the cytoplasmic analogue of smooth and skeletal muscle myosin. AIMS AND METHODOLOGY: Because the activity of myosin II is accelerated by phosphorylation of myosin II on its regulatory light chain (RLC) by myosin light chain kinase (MLCK), we used two specific MLCK inhibitors, ML-7 and ML-9, for suppression of motility and adhesion of PC cell lines. RESULTS: Both drugs were potent inhibitors, as measured by in vitro motility assay and adhesion assay. When treated with the same concentration of ML-7, the PC cells were rounded up, and the number of stress fibers was reduced markedly. The in vitro migration and adhesion of PC cells were inhibited by ML-7 and ML-9 in a dose-dependent manner, supporting a specific and competitive inhibition of MLCK by these drugs. The inhibition occurred at nontoxic concentrations. CONCLUSIONS: These results highlight the importance of myosin II in the invasion and metastasis of PC cells and suggest the possibility that blocking of myosin II activity by a specific MLCK inhibitor may be a therapeutic strategy for preventing the invasion and metastasis of PC.

Azepines↗
PubMed2002

Activation of adenosine A2a receptor pathway reduces leukocyte infiltration but enhances edema formation in rat caerulein pancreatitis.

INTRODUCTION: Adenosine plays important roles in a variety of pathophysiologic conditions through receptor-mediated mechanisms. Recent studies have shown that adenosine exerts potent anti-inflammatory properties that are chiefly brought about through the occupancy of the A2a receptor. AIM: To examine the effect of A2a receptor stimulation or inhibition on the pathologic findings during acute pancreatitis. METHODOLOGY: Rats were randomized into three groups and received a selective A2a receptor agonist CGS-21680 (CGS), a selective A2a antagonist 3,7-dimethyl-1-[2-propynyl]-xanthine (DMPX), or saline. Thirty minutes after the injection, acute pancreatitis was produced in the rats by seven intraperitoneal injections of caerulein. The severity of acute pancreatitis was evaluated by serum amylase activity, pancreas myeloperoxidase (MPO) activity, Evans blue extravasation, and pathologic changes of the pancreas. In addition, we investigated the effects of CGS on the pathologic findings of caerulein pancreatitis induced in neutrophil-depleted rats. RESULTS: Administration of caerulein produced hyperamylasemia and morphologic changes of the pancreas including interstitial edema, acinar cell vacuolization, and infiltration of inflammatory cells. In CGS-treated rats, the pancreatic edema and the Evans blue extravasation were aggravated significantly compared with those of saline-treated rats, whereas leukocyte infiltration and MPO activity of the pancreas were decreased. In contrast to CGS, administration of DMPX ameliorated the pancreatic edema and Evans blue extravasation. Treatment with CGS accelerated the pancreatic edema in pancreatitis even after the depletion of neutrophils. CONCLUSION: The activation of adenosine A2a receptors modulates the pathology of acute pancreatitis through at least two diverse properties. One is an anti-inflammatory effect involving neutrophils, and the other is a propagating effect for pancreatic edema formation. The actions of the A2a receptor pathways are unique, and they may have an important role in the progression of acute pancreatitis.

Adenosine↗
PubMed2002

Ligands of peroxisome proliferator-activated receptor-gamma induce apoptosis in AR42J cells.

INTRODUCTION: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor that controls growth, differentiation, and inflammation in different tissues. Roles of PPAR-gamma activation in pancreatic acinar cells are poorly characterized. AIMS: To examine the effects of PPAR-gamma activation on the induction of apoptosis in rat pancreatic AR42J cells. METHODOLOGY: AR42J cells were treated with ligands of PPAR-gamma, and induction of apoptosis was evaluated by cell viability, DNA-fragmentation, and flow cytometry. RESULTS: Treatment of the cells with ligands of PPAR-gamma (15-deoxy-open triangle12,14-prostaglandin J2 or troglitazone) induced apoptosis in a dose-dependent manner. Troglitazone-induced apoptosis was not blocked by inhibitors of caspases (acetyl-DEVD-aldehyde and benzoyloxycarbonyl-VAD-fluoromethylketone). Troglitazone induced the expression of pancreatitis-associated protein-1 and clusterin mRNAs. Troglitazone activated c-Jun NH2-terminal kinase/stress-activated protein kinase, but inhibited the activation of extracellular signal-regulated kinases 1/2. Troglitazone did not activate NF-kappaB, suggesting a role of NF-kappaB-independent pathways. In AR42J cells and isolated pancreatic acini, PPAR-gamma gene and protein were detected. In addition, troglitazone increased the PPAR-dependent transcriptional activity, suggesting that PPAR-gamma is functional in AR42J cells. CONCLUSION: These results indicate that activation of PPAR-gamma induces apoptosis in AR42J cells and imply that PPAR-gamma may be a potential therapeutic target of pancreatic inflammation, because of its anti-inflammatory effects in addition to its proapoptotic effects.

Amino Acid Chloromethyl Ketones↗
PubMed2002

Expression of ROCK-1 in human pancreatic cancer: its down-regulation by morpholino oligo antisense can reduce the migration of pancreatic cancer cells in vitro.

INTRODUCTION: Invasion and metastasis of cancer cells require cell motility and adhesion. The small GTPase Rho and one of its effector molecules ROCK regulate cytoskeleton and actomyosin contractility, and play a crucial role in cell adhesion and motility. Results of previous studies showed that the elevated activity of ROCK-1, one of the isomers of ROCK kinases, led to an increase in the activity of invasion and metastasis of cancer cell lines. AIM: To investigate the importance of ROCK-1 in cancer invasion and metastasis. METHODOLOGY: We investigated the expression of ROCK-1 in two cancer cell lines and 31 human pancreatic tissues (21 pancreatic cancers [PC] and 10 histologically normal tissues) by immunoblotting and immunohistochemistry. We also examined by haptotaxis assay whether the migratory activity of PC cells could be suppressed by treatment with the morpholino antisense oligonucleotide in vitro. RESULTS: The expression of ROCK-1 was found in 18 of 21 PC tissues (85.7%), but not in normal pancreatic tissues by immunoblotting and immunohistochemistry. Antisense oligo against ROCK-1 significantly inhibited the haptotaxis of Panc-1 in a dose-dependent manner, compared with the control oligo. CONCLUSION: These results suggest that ROCK-1 may contribute to pancreatic cancer cell invasion and/or metastasis by facilitating cancer cell migration.

Cell Movement↗
PubMed2002

Activated rat pancreatic stellate cells express intercellular adhesion molecule-1 (ICAM-1) in vitro.

INTRODUCTION: Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic fibrosis. AIMS: To examine the role of PSCs in pancreatic inflammation by determining whether activated PSCs express intercellular adhesion molecule-1 (ICAM-1). METHODOLOGY: Culture-activated rat PSCs were treated with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), ethanol, or acetaldehyde. ICAM-1 expression was analyzed by flow cytometry. The induction of mRNA was assessed by Northern blot analysis. The binding activity of transcription factors was examined by electrophoretic mobility shift assay. The activation of mitogen-activated protein kinases was assessed by Western blotting with use of antiphosphospecific antibodies. The adhesion of MOLT-4 cells to activated PSCs was also assessed. RESULTS: Culture-activated PSCs expressed ICAM-1. The expression was increased in response to IL-1 beta and TNF-alpha but not to alcohol, with comparable mRNA induction. IL-1 beta and TNF-alpha increased the nuclear factor-kappa B (NF-kappa B)-specific and activator protein-1-specific DNA binding activity, whereas the NF-IL6 activity was not altered. Alcohol did not increase NF-kappa B binding activity. IL-1 beta and TNF-alpha activated extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinase. Inducible ICAM-1 expression was blocked by pyrrolidine dithiocarbamate, a specific inhibitor of NF-kappa B activation, but not by inhibitors of mitogen-activated protein kinase pathways. IL-1 beta and TNF-alpha increased the ICAM-1-mediated binding of MOLT-4 cells to activated PSCs, indicating a role of ICAM-1 in the adhesion of leukocytes to PSCs. CONCLUSION: Our results suggest that activated PSCs express ICAM-1 mainly through the activation of NF-kappa B, thus playing a role in the pathogenesis of pancreatic inflammation.

Acetaldehyde↗
PubMed2002

Human leukocyte antigen-DR expression on peripheral monocytes as a predictive marker of sepsis during acute pancreatitis.

INTRODUCTION: The mortality associated with severe acute pancreatitis is still high, and death in the later stage of the disease is chiefly due to bacterial infection and sepsis. However, objective parameters for the risk of sepsis in acute pancreatitis have not been established. AIM: To investigate the value of human leukocyte antigen-DR (HLA-DR) on peripheral monocytes for predicting the development of sepsis during acute pancreatitis. METHODOLOGY: The expression of HLA-DR on peripheral monocytes was measured in 64 patients by flow cytometry at admission and 7 and 14 days after the onset of acute pancreatitis. Twenty-eight patients with severe acute pancreatitis and 36 with mild acute pancreatitis, as determined by the Atlanta classification, were enrolled. RESULTS: Six patients had sepsis, and two of them died during the hospital stay. At admission, the percentage of HLA-DR-expressing cells in the monocyte population was significantly lower in the patients who had sepsis in the later course than in the patients who did not have sepsis. A percentage lower than 80% at admission was observed in 17 patients, and the patients who had persistently low percentages of HLA-DR-expressing monocytes throughout the observation period had sepsis in the later clinical course, whereas the patients in whom expression recovered to the normal range were spared the development of sepsis. CONCLUSION: In acute pancreatitis, the low percentage of HLA-DR-expressing cells in the monocyte population is a reliable predictor of the development of sepsis. Monitoring of monocyte HLA-DR expression may be a useful marker for identifying the patients who are at high risk of sepsis in acute pancreatitis.

Acute Disease↗
PubMed2002

Three-dimensional reconstruction and fractal geometric analysis of serrated adenoma.

Serrated adenoma (SA) is a relatively newly defined entity of colorectal neoplasm first characterized by Longacre and Fenoglio-Preiser in 1990. This lesion is characterized by a complicated serrated edge of crypts. In this study, we performed three-dimensional (3-D) reconstruction, including 3-D distribution patterns of Ki-67-positive cells and fractal dimension of SA, in order to evaluate the nature of the complicated architecture, including its possible morphogenesis. We studied nine colonoscopic polypectomy specimens including three SAs, three tubular adenomas (TAs), and three hyperplastic polyps (HPs). Sixty serial tissue sections per case were stained alternately with hematoxylin and eosin (H&E) and Ki-67 immunostain. Each serial image was then digitized for 3-D computer analysis and the distribution pattern of Ki-67-positive cells was evaluated. Ki-67-immunostained sections were also subjected to 2-D quantitative morphometric study. In addition, the fractal dimensions of images from H&E-stained sections were examined using a box-counting method. Results of the 3-D reconstruction study demonstrated that glandular budding and branching were more frequent in SA than in TA or HP. These findings were confirmed quantitatively by the results of fractal geometric analysis of these polyps (fractal dimension:1.34 +/- 0.08 for SA, 1.23 +/- 0.07 for TA, and 1.28 +/- 0.12 for HP). Ki-67-positive cells in HP were localized mainly in the bottom of crypts and those in TA were diffusely distributed, while Ki-67-positive cells in SA were mainly aggregated in the depressed sites of serrated epithelia. These findings were also confirmed quantitatively using 2-D morphometry. These distribution patterns of the proliferative zone of SA are considered to contribute to the formation of the characteristic serrated epithelia and the complicated morphological appearance of SA.

Adenoma↗
PubMed2002

Alcohol activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells.

Alcohol is a major cause of both acute and chronic pancreatitis. Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic inflammation and fibrosis. Herein, we examined the effect of ethanol and acetaldehyde on the activation of transcription factors and mitogen-activated protein (MAP) kinases in PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. PSCs were treated with ethanol and acetaldehyde at clinically relevant concentrations (50 mM and 200 microM, respectively). Ethanol and acetaldehyde activated activator protein-1 but not nuclear factor-kappaB. In addition, they activated three classes of MAP kinases: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 MAP kinase. Ethanol- and acetaldehyde-induced activation of activator protein-1 and MAP kinases was blocked by the antioxidant N-acetyl-cysteine, suggesting a role of oxidative stress in the signal transduction. Ethanol and acetaldehyde induced alpha1(I) procollagen gene expression but did not induce intercellular adhesion molecule-1 and monocyte chemoattractant protein-1. The acetaldehyde-induced increase of alpha1(I) procollagen gene expression was inhibited by the p38 MAP kinase inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580) but not by the MAP kinase inhibitor 2'-amino-3'-methoxyflavone (PD98059). Specific activation of these signal transduction pathways may play a role in the pathogenesis of alcohol-induced pancreatic injury.

Acetaldehyde↗
PubMed2002

Establishment and characterization of a simian virus 40-immortalized rat pancreatic stellate cell line.

Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line would be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish an immortalized cell line of rat PSCs. PSCs were isolated from the pancreas of male Wistar rats, and the simian virus 40 T antigen was introduced to PSCs by retrovirus-mediated gene transfer. This procedure yielded an actively growing cell line, designated as SAM-K. This cell line has been passaged repeatedly for almost 2 years, and is thus likely immortalized. SAM-K cells retained morphological characteristics of primary PSCs, and expressed alpha-smooth muscle actin, glial fibrillary acidic protein, type I collagen, fibronectin, and prolyl hydroxylases. The level of p53 expression was very high in SAM-K cells. Proliferation of SAM-K cells was stimulated by serum and platelet-derived growth factor-BB. Interleukin-1beta (IL-1beta) activated nuclear factor-kappaB, activator protein-1, and three classes of mitogen-activated protein (MAP) kinases: extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase, and p38 MAP kinase. IL-1beta induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1, both of which were abolished in the presence of pyrrolidine dithiocarbamate, a specific inhibitor of nuclear factor-kappaB activation. IL-1beta-induced monocyte chemoattractant protein-1 was partially inhibited by specific inhibitors of MAP kinase kinase (U0126) and of p38 MAP kinase (SB203580) whereas intercellular adhesion molecule-1 expression was not altered by the inhibitors. Thus, SAM-K would be useful for in vitro studies of cell biology and signal transduction of PSCs.

Animals↗
PubMed2001

Ligands of peroxisome proliferator-activated receptor-gamma block activation of pancreatic stellate cells.

Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-activated transcription factor which controls growth, differentiation, and inflammation in different tissues. Roles of PPAR-gamma activation in PSCs are poorly characterized. Here we examined the effects of PPAR-gamma ligands on the key parameters of PSC activation. PSCs were isolated from rat pancreas tissue, and used in their culture-activated, myofibroblast-like phenotype. Activation of PPAR-gamma was induced with 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) or with troglitazone. Expression of PPAR-gamma was predominantly localized in the nuclei, and PPAR-gamma was transcriptionally active after ligand stimulation. PPAR-gamma ligands inhibited platelet-derived growth factor-induced proliferation. This effect was associated with inhibition of cell cycle progression beyond the G1 phase. PPAR-gamma ligands decreased alpha-smooth muscle actin protein expression and alpha1(I) procollagen and prolyl 4-hydroxylase(alpha) mRNA levels. Activation of PPAR-gamma also resulted in the inhibition of inducible monocyte chemoattractant protein-1 expression. 15d-PGJ2, but not troglitazone, inhibited the degradation of IkappaB-alpha and consequent NF-kappaB activation. In conclusion, activation of PPAR-gamma inhibited profibrogenic and proinflammatory actions in activated PSCs, suggesting a potential application of PPAR-gamma ligands in the treatment of pancreatic fibrosis and inflammation.

Actins↗