UMLS:C0030305 - FACTA Search

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Query: UMLS:C0030305 (pancreatitis)
16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pancreatitis-associated protein (PAP) is a lectin-related secretory protein present in small amounts in the rat pancreas and overexpressed during the acute phase of pancreatitis. On the other hand, PAP is constitutively expressed in the intestinal tract but not in other tissues. We cloned from a pancreatic cDNA library two overlapping cDNAs encoding a protein structurally related to PAP. This second PAP, which was called PAP II, was the same size as the original PAP (PAP I) and showed 74.3% amino acid homology. Studies on gene expression demonstrated that PAP II mRNA concentration increased within 6 h following induction of pancreatitis, reached maximal levels (> 200 times control values) at 24-48 h, and decreased thereafter, similar to PAP I. However, PAP II mRNA could not be detected in the intestinal tract or in other tissues. We also isolated a PAP II genomic DNA fragment which was characterized over 2.7 kb of gene sequence and 1.9 kb of 5' flanking sequence. The 5' end of the coding sequence was determined by primer extension of the PAP II mRNA. The PAP II coding sequence spanned six exons separated by five introns. Several potential regulatory elements were identified in the promoter region, including two glucocorticoid-response elements and one IL-6-response element. Antibodies raised to a synthetic peptide of PAP II detected a single band in Western blot analysis of the pancreatic secretory proteins from rats with pancreatitis, with a M(r) compatible with the theoretical M(r) of PAP II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of a second rat pancreatitis-associated protein. Messenger RNA cloning, gene structure, and expression during acute pancreatitis. 836 91

The biological significance and function of pancreatitis-associated protein (PAP), identified in 1984 as a new secretory protein appearing during pancreatitis, remain to be elucidated. The purpose of this study was to evaluate the presence of PAP in pancreatic tissue upon its exposure to chlorophenylalanine methyl ester (CPME), a drug known to disrupt the regulated secretory pathway of acinar cells, an experimental condition that differs from acute pancreatitis. Pancreatic tissues were processed either for immunocytochemistry or for Northern blot analysis at 17-72 h after a single intraperitoneal injection of CPME in rats. Pancreatic acinar cells displayed endoplasmic reticulum intracisternal crystals consisting of an abnormal aggregation of secretory proteins as well as a sub-population of small and aberrant secretory granules. PAP mRNA was strongly increased at 17-24 h after CPME treatment, and PAP immunoreactivity was detected along the regulated secretory pathway, particularly in the small and aberrant secretory granules at these same time points. Levels of PAP and PAP mRNA decreased gradually, to become undetectable after 72 h. Autoradiographic experiments demonstrated that these small aberrant granules stored preferentially newly synthesized proteins. Our results indicate that the induction of PAP is not exclusive to acute pancreatitis since it appears in pancreatic cells as a response to certain insults and is secreted preferentially through a particular population of small aberrant granules.
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PMID:Presence of pancreatitis-associated protein in pancreatic acinar cells of rats treated with chlorophenylalanine methyl ester. 882 82

The pancreatitis-associated proteins (PAPs) are major pancreatic secretory proteins during acute pancreatitis. However, mechanisms of regulation of PAP gene expression are poorly understood, and there is a lack of information regarding mouse PAP gene expression. Herein, we employed Northern blotting and RNase protection assays to measure mouse PAP-I mRNA levels in the normal pancreas and intestine, and in the pancreas during caerulein-induced acute pancreatitis. Unexpectedly, we found that mouse PAP-I mRNA levels are constitutively high in the adult pancreas, as well as in the small intestine. Furthermore, mouse pancreatic PAP-I mRNA levels are rapidly and dramatically down-regulated (3 h) after the initiation of caerulein injections, but slowly return to high levels by 72 h. Interestingly, we found that pancreatic PAP-I mRNA levels are also transiently and dramatically down-regulated after L-buthionine-[S,R]-sulfoximine administration. Thus, a correlation between PAP-I mRNA levels and glutathione levels in the mouse pancreas was demonstrated.
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PMID:Regulation of mouse pancreatitis-associated protein-I gene expression during caerulein-induced acute pancreatitis. 888 77

1. The time course of iron overload of the pancreas in hypotransferrinaemic mice maintained on a standard rodent diet was compared with biochemical and histological markers of tissue damage. 2. Pancreatic iron levels increased linearly from weaning till 9 months of age [73.3 nmol/mg of tissue (SEM 9.9; n = 5) compared with 0.9 nmol/mg of tissue (SEM 0.1; n = 4) in age-matched controls] then decreased linearly till at least 18 months of age. 3. Investigation of tissue distribution of newly absorbed radioiron suggested that significant redistribution of iron from liver to pancreas (rather than direct dietary iron sources) must be invoked to explain the rate of pancreatic iron loading in hypotransferrinaemic mice. 4. Pancreatic epithelial cells first showed altered morphology at 9 months of age. At 12 months of age, the pancreatic epithelium had developed a micronodular appearance, with large numbers of acini replaced by atrophic, degenerated acinar cells. Increased collagen fibre deposition was evident by trichrome staining and by electron microscopy. Biochemical markers of pancreatitis (serum lipase, tissue pancreatitis-associated protein mRNA) were elevated before 9 months of age, whereas the levels of pancreatic amylase mRNA declined from 9 months of age. 5. The data suggest that iron loading of hypotransferrinaemic mouse pancreas proceeds up to a threshold level at 9 months of age followed by a progressive atrophy of secretory epithelium. The hypotransferrinaemic mouse pancreas is a useful model system for investigation of parenchymal cell damage by iron.
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PMID:Time-course of iron overload and biochemical, histopathological and ultrastructural evidence of pancreatic damage in hypotransferrinaemic mice. 948 91

The pancreatitis-associated protein (PAP) was investigated in patients with hereditary and chronic alcoholic pancreatitis. Blood levels of pancreatic enzymes and PAP were measured in nine families with hereditary pancreatitis; in three of them, the mutation N21I, and in six, the R117H variant of the cationic trypsinogen were present. In all family members, similar to controls, only normal values of the PAP were found. There was no evidence for polymorphism of the PAP gene in patients with hereditary or alcoholic pancreatitis. Immunohistochemically PAP was detected in the apical parts of the acinar cells but not in ducts, interstitial tissue, islets, or blood vessels. Intensity of PAP labeling was directly related to the deterioration of the acinar units, and its concentration was inversely related to chymotrypsinogen immunoreactivity in the same tissue. Similar immunohistochemical findings were present in chronic alcoholic and hereditary pancreatitis. We conclude that there is a lack of PAP polymorphism in hereditary and alcoholic pancreatitis and that expression of the PAP in both groups of patients is related to the degree of cellular damage of the pancreas.
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PMID:The pancreatitis-associated protein in hereditary and chronic alcoholic pancreatitis. 1050 55

The human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein (HIP/PAP) gene was previously identified because of its increased expression in primary liver cancers and during the acute phase of pancreatitis. In normal tissues, HIP/PAP is expressed both in endocrine and exocrine cells of the intestine and pancreas. HIP/PAP is a lactose binding C-type lectin which acts as an adhesion molecule for rat hepatocytes. The aim of the work was to study the HIP/PAP secretory pathway and to produce high levels of HIP/PAP in the milk of lactating transgenic mice. In view of its lactose C-type lectin properties, we have studied the consequences of the expression of HIP/PAP on mammary epithelial cells. In homozygous mice, production reached 11.2 mg.mL-1 of milk. High levels of soluble and pure HIP/PAP (18.6 mg) were purified from 29 mL of milk. The purified protein was sequenced and the N-terminal amino acid of the mature HIP/PAP was identified as Glu27, thus localizing the site of cleavage of the signal peptide. The HIP/PAP transgene was only expressed in the mammary gland of lactating transgenic mice. HIP/PAP was detected by immunofluorescence in the whole gland, but labelling was heterogeneous between alveolar clusters, with strongly positive sparse cells. Using immuno electron microscopy, HIP/PAP was observed in all the compartments of the secretory pathway within the mammary epithelial cells. We provide evidence that HIP/PAP is secreted through the Golgi pathway. However, the number of distended Golgi saccules was increased when compared to that found in wild-type mouse mammary cells. These modifications could be related to HIP/PAP C-type lectin specific properties.
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PMID:High expression of the human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein (HIP/PAP) gene in the mammary gland of lactating transgenic mice. Secretion into the milk and purification of the HIP/PAP lectin. 1071 97

A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases. In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases. Scanning and transmission electron microscopy indicate that activated thread proteins polymerize into highly organized fibrillar structures with helical configurations. Through bundling, branching, and extension processes, these fibrillar structures form dense matrices that span large topological surfaces. These findings suggest that PSP/reg and PAP I and III isoforms consist of a family of highly regulated soluble secretory stress proteins, which, upon trypsin activation, convert into a family of insoluble helical thread proteins. Dense extracellular matrices, composed of helical thread proteins organized into higher ordered matrix structures, may serve physiological functions within luminal compartments in the exocrine pancreas.
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PMID:A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. 1127 30

Interleukin-22 (IL-22) (also reported as IL-10-related T cell-derived inducible factor, IL-TIF) is a recently identified cytokine found to signal through a receptor comprising the class II cytokine receptor family members IL-10Rbeta/CRF2-4 and IL-22R. Previous work has established that IL-10Rbeta, also a component of the IL10R complex, exhibits a broad distribution of mRNA expression. Here, we observe that IL-22R exhibits a restricted expression pattern, with highest levels of mRNA expression in pancreas and detectable expression in multiple other tissues, particularly liver, small intestine, colon, and kidney. We find that isolated primary pancreatic acinar cells and the acinar cell line 266-6 respond to IL-22 with activation of Stat3 and changes in gene transcription. IL-22 mediates robust induction of mRNA for pancreatitis-associated protein (PAP1)/Reg2 and osteopontin (OPN). PAP1 is a secreted protein related to the Reg family of trophic factors and was initially characterized as a protein elevated in pancreatitis. In vivo injection of IL-22 resulted in rapid induction of PAP1 in pancreas, a response not observed in mice deficient in IL-10Rbeta. These results support the conclusion that IL-10Rbeta is a required common component of both the IL-10 and IL-22 receptors and suggest that IL-22 may play a role in the immune response in pancreas.
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PMID:Acinar cells of the pancreas are a target of interleukin-22. 1179 62

New biomarkers of pancreatic adenocarcinoma are needed to improve the early detection of this deadly disease. We performed surface enhanced laser desorption ionization (SELDI) mass spectrometry using ProteinChip technology (Ciphergen Biosystems, Fremont, CA) to screen for differentially expressed proteins in pancreatic juice. Pancreatic juice samples obtained from patients undergoing pancreatectomy for pancreatic adenocarcinoma were compared with juice samples from patients with other pancreatic diseases. We identified a peak approximately 16,570 daltons present in the pancreatic juice from 10/15 (67%) of the patients with pancreatic adenocarcinoma and in the pancreatic juice from 1/7 (17%) of the patients with other pancreatic diseases. Using a ProteinChip immunoassay, we identified this differentially expressed protein as hepatocarcinoma-intestine-pancreas/pancreatitis-associated-protein I (HIP/PAP-I), a protein released from pancreatic acini during acute pancreatitis and overexpressed in hepatocellular carcinoma. We then quantified by ELISA the pancreatic juice HIP/PAP-I levels in 43 patients (28 with pancreatic adenocarcinoma, 15 with other pancreatic diseases) and the serum HIP/PAP-I levels in 98 patients (53 with pancreatic adenocarcinoma, 45 with other pancreatic diseases or healthy individuals). HIP/PAP-I levels were significantly higher in both the pancreatic juice (P < 0.001) and in the serum (P < 0.001) of patients with pancreatic adenocarcinoma compared with the control group. HIP/PAP-I levels were approximately 1000-fold higher in pancreatic juice compared with serum and the magnitude of the difference between the pancreatic adenocarcinoma group and the control group was greater in the pancreatic juice samples (143.75 +/- 235.52 microg/ml versus 6.04 +/- 7.59 microg/ml) than in the serum samples (99.96 +/- 140.66 ng/ml versus 35.25 +/- 28.44 ng/ml). In our study, patients with pancreatic juice HIP/PAP-I levels > or= 20 microg/ml were 21.9 times (95% confidence interval, 3.5-136.5; P < 0.001) more likely to have pancreatic adenocarcinoma than patients with levels <20 microg/ml. Immunolabeling of tissue sections revealed that the HIP/PAP-I protein was strongly expressed in acini adjacent to the invasive adenocarcinoma, but it was only rarely (1/30; 3%) expressed in the neoplastic epithelium, which suggests that the main source of HIP/PAP-I release in the pancreatic juice is acini. This low level of HIP/PAP-I expression in pancreatic adenocarcinoma was confirmed by reverse transcription-PCR: only 1 (5%) of 19 pancreatic cancer cell lines expressed HIP/PAP-I transcripts. Taken together, these data suggest that pancreatic juice measurement of HIP/PAP-I may help to identify patients with pancreatic adenocarcinoma.
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PMID:Identification of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by protein biochip technology. 1191 67

The pancreatitis-associated protein (PAP) is a pancreatic stress protein overexpressed during acute pancreatitis, a disease often accompanied by lung inflammation. We investigated whether PAP was involved in the occurrence of this remote complication of pancreatitis and whether the liver might be implicated in the process. PAP was injected into the vena cava of rats (40 or 400 micro g/kg body weight). For comparison, pancreatitis was induced in rats by intraductal administration of sodium taurocholate. Three hours later, parameters of inflammation and mRNA concentrations of TNFalpha, P-selectin, heat shock protein (HSP)-70, and extracellular superoxide dismutase (EC-SOD) were monitored in lung and liver. Significant increases in P-selectin expression, neutrophil infiltration, and oxidative stress revealed that PAP treatment induced lung inflammation in rats and exacerbated inflammation in animals with pancreatitis. Plasma TNFalpha level was increased and TNFalpha mRNA was strongly overexpressed in liver, with concomitant activation of NF-kappaB; in situ hybridization revealed that TNFalpha overexpression was mainly located to hepatocytes. Lung inflammation induced by PAP could be prevented by injection of anti-TNFalpha antibodies. It was concluded that, during pancreatitis, PAP released by the pancreas could mediate lung inflammation through induction of hepatic TNFalpha expression and subsequent increase in circulating TNFalpha.
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PMID:The pancreatitis-associated protein induces lung inflammation in the rat through activation of TNFalpha expression in hepatocytes. 1257 42

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