Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic and lung inflammation during acute pancreatitis is a poorly understood, but clinically important, phenomenon. The proto-oncogene Tpl2 (tumor progression locus-2) has recently been shown to have important immunomodulatory effects on some inflammatory processes, but its importance to pancreatitis has not been previously examined. Our studies were designed to (a) define the effects of Tpl2 on pancreatic and lung inflammation during pancreatitis and (b) identify mechanisms and cell types responsible for those effects. We examined pancreatitis-associated Tpl2 effects in wild type and Tpl2(-/-) mice subjected to either secretagogue-induced or bile salt-induced pancreatitis. To determine the myeloid or non-myeloid lineage of cells responsible for the Tpl2 effects, we used Tpl2(-/-) chimeric mice generated by lethal irradiation followed by bone marrow transplantation. Mechanisms responsible for the effects of Tpl2 ablation on caerulein-induced proinflammatory events were evaluated under in vivo and in vitro conditions using the techniques of electrophoretic mobility shift assay, immunoblot analysis, and quantitative reverse transcription-PCR. We found that Tpl2 ablation markedly reduced pancreatic and lung inflammation in these two dissimilar models of pancreatitis, but it did not alter pancreatic injury/necrosis in either model. The reduction in caerulein-induced pancreatic inflammation is dependent upon Tpl2 ablation in non-myeloid cells and is associated with both in vivo and in vitro inhibition of MEK, JNK, and AP-1 activation and the expression of MCP-1, MIP-2, and interleukin-6. Non-myeloid cell expression of Tpl2 regulates pancreatic inflammation during pancreatitis by mediating proinflammatory signals and the generation of neutrophil chemoattracting factors.
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PMID:Tumor progression locus-2 is a critical regulator of pancreatic and lung inflammation during acute pancreatitis. 1753 24

Angiotensin II is a key mediator of inflammation, and nuclear factor-kappaB (NF-kappaB) plays a critical role in various inflammatory diseases, including acute pancreatitis (AP). This study sought to elucidate the mechanism mediating angiotensin II involvement in angiotensin II type 1 (AT1) receptor-mediated NF-kappaB activation, and ultimately in proinflammatory actions of AP pathogenesis. A rat model of obstructive pancreatitis was induced by ligation of the common biliopancreatic duct. Pancreatic injury was determined by assessing pancreatic histology, myeloperoxidase activity, and serum interleukin-6. Protein levels of pancreatic angiotensinogen and AT1 receptor as well as NF-kappaB inhibitory subunits (IkappaBalpha and IkappaBbeta) and phospho-NF-kappaB p65, kappaB-related proteins (intercellular adhesion molecule-1, cyclooxygenase-2, and interleukin-1), and NADPH oxidase isoforms p67 and p22 were examined by Western blot. Nuclear kappaB binding activity and degree of oxidative stress were determined by electrophoretic mobility shift assay and glutathione/nitrotyrosine examination, respectively. The effects of losartan, an AT1 receptor antagonist, on NF-kappaB-mediated proinflammatory actions were also assessed. Induction of AP was associated with a time-dependent increase in pancreatic angiotensinogen levels. AT1 receptor blockade with losartan improved the pancreatic histological damage, myeloperoxidase activity, and serum interleukin-6. Losartan treatment also reduced AP-associated depletion of IkappaBbeta and elevation of phospho-NF-kappaB p65 protein expression as well as the enhanced nuclear kappaB binding activity and elevated levels of kappaB-related proteins. In addition, losartan treatment suppressed pancreatic glutathione and nitrotyrosine levels, which were consistent with decreased NADPH oxidase expression. These data provide substantial evidence that angiotensin II is involved in AT1 receptor-mediated NADPH oxidase-dependent NF-kappaB activation; thus, it might ultimately promote proinflammatory actions during AP pathogenesis.
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PMID:Angiotensin II type 1 receptor-dependent nuclear factor-kappaB activation-mediated proinflammatory actions in a rat model of obstructive acute pancreatitis. 1761 60

The aim of this study was to investigate the influence of enalaprilat on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in a significant increase in the mortality rate, pancreatic necrosis, serum activity of amylase, alanine aminotransferase (ALT), and interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, and tissue activity of myeloperoxidase (MPO) and maondialdehyde (MDA) in the pancreas and lung, and a significant decrease in concentrations of calcium, blood pressure, urine output and p0(2). The use of enalaprilat inhibited the changes in urine output, blood pressure, serum concentration of urea, p0(2), and tissue activity of MPO and MDA in the pancreas and lungs. It reduced the mortality and pancreatic damage. Enalaprilat demonstrated a beneficial effect on the course of ANP in rats; therefore, it may be used in the treatment of acute pancreatitis.
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PMID:Effects of enalaprilat on acute necrotizing pancreatitis in rats. 1765 97

Acute pancreatitis (AP) activates the systemic inflammatory response and is potentially lethal. Recent studies demonstrated that pancreatic enzymes could induce cytokine expression via Toll-like receptor 4 (TLR4) signal pathway, indicating a possible role of TLR4 in local pancreatic injury and systemic inflammatory response. Emodin, an anthraquinone derivative from Radix et Rhizoma Rhei, and baicalin, a flavone from Scutellaria baicalensis Georgi, both have been reported to possess anti-inflammatory activities. In present study, we investigated the combined effect of emodin and baicalin on pancreatic damage and pancreatitis associated lung injury, as well as tissue TLR4 expression in the setting of AP. The results showed that combination of emodin and baicalin significantly reduced serum amylase, tumor necrosis factor-alpha and interleukin-6, attenuated pancreatic and pulmonary damage, also suppressed TLR4 expression in pancreas and lung. It could be speculated that amelioration of pancreatic and pulmonary damage by emodin and baicalin might contribute, in part at least, to the suppression of TLR4 expression. The present study provides beneficial evidence as to simultaneous treatment for AP, and also suggests an important role of TLR4 in pathophysiology of AP.
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PMID:Up-regulation of Toll-like receptor 4 was suppressed by emodin and baicalin in the setting of acute pancreatitis. 1834 29

Gabexate mesilate is a synthetic protease inhibitor that is effective for acute pancreatitis. The effect of gabexate mesilate in influenza pneumonia in mice was investigated by examining the changes in pulmonary inflammatory cytokines and chemokines. Pathological changes in the lungs of treated mice were extremely mild, compared with changes in infected, untreated mice. Intrapulmonary levels of interleukin-6 and macrophage inflammatory protein-2 decreased in treated mice compared with untreated mice, despite similar viral titres in the lungs. Survival terms for treated and untreated groups were similar. These data indicate that gabexate mesilate has beneficial effects on influenza pneumonia, which may be due to the modulation of inflammatory cytokine/chemokine responses.
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PMID:Gabexate mesilate suppresses influenza pneumonia in mice through inhibition of cytokines. 1838 Sep 43

Activation of nuclear factor kappaB (NF-kappaB) and caspases may greatly amplify inflammation and cell damage in addition to that directly exerted by free radicals. Since reactive oxygen species (ROS) are involved in acute pancreatitis, we studied whether the administration of chondroitin-4-sulphate (C4S), in addition to its antioxidant activity, was able to modulate NF-kappaB and caspase activation in an experimental model of caerulein-induced acute pancreatitis in mice. Hyperstimulating doses of caerulein (50 microg/ kg), five injections per mouse given at hourly intervals produced the following: high serum lipase and amylase activity; lipid peroxidation, evaluated by 8-isoprostane concentrations; loss of antioxidant defenses such as glutathione reductase (GR) activity; NF-kappaB activation and loss of cytoplasmic IkappaBalpha protein; increases in tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), caspase-3, and caspase-7 gene expression and their related protein; accumulation and activation of neutrophils in the damaged tissue, evaluated by elastase (ELA) determination; and pancreatic injury, evaluated by histologic analysis. Pretreatment of mice with different doses of C4S, given 1 hr before caerulein injections and 1 and 2 hrs after the last caerulein injection, reduced lipid peroxidation, inhibited NF-kappaB translocation and cytoplasmic IkappaBalpha protein loss, decreased TNF-alpha, IL-6, and caspase gene expression and their related protein levels, limited endogenous antioxidant depletion, and reduced tissue neutrophils accumulation and tissue damage. Since molecules with antioxidant activity can block NF-kappaB and apoptosis activation, we suggest that C4S administration is able to block NF-kappaB and caspase activation by reducing the oxidative burst.
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PMID:Chondroitin-4-sulphate reduced oxidative injury in caerulein-induced pancreatitis in mice: the involvement of NF-kappaB translocation and apoptosis activation. 1840 39

To gain insight into the processes by which severe acute pancreatitis induced apoptosis takes place in the liver, and to observe the protective effect of resveratrol on hepatic injury, a rat model of severe acute pancreatitis was induced by administering 4% sodium taurocholate through the common biliopancreatic duct. Pancreatic and hepatic injury was assessed by histology. Serum ALT (alanine aminotransferase), AST (aspartate aminotransferase) and total bilirubin were determined by reaction rate assay, and the serum levels of TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) were detected by ELISA (enzyme linked immunosorbent assay). We investigated cytochrome c released from mitochondria and used the RT-PCR (reverse transcription PCR), Western blot technique to evaluate Bax, Bcl-2, and caspase-3 expression levels in hepatic tissue over the time course of apoptosis. Changes in hepatic cell mitochondrial membrane potential were observed by confocal laser scanning microscopy. The majority of cytochrome c release occurred early in apoptosis from mitochondria, which undergo gradual hepatic impairment. The released cytochrome c can be reduced by resveratrol through both up-regulation of Bcl-2 and down-regulation of Bax and caspase-3. These data provide substantial evidence that apoptosis is involved in hepatic injury during the severe acute pancreatitis process and that resveratrol can ameliorate the situation, thus protecting liver function in rats with severe acute pancreatitis.
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PMID:Resveratrol ameliorates hepatic injury via the mitochondrial pathway in rats with severe acute pancreatitis. 1897 15

Improving the outcome of acute pancreatitis through prognostic markers has been a matter of ample research. We evaluate the clinical usefulness of four serum markers in comparison to Ranson's score. Serum measurements of C-reactive protein (CRP), interleukin-6, -10 (IL-6, IL-10), and pancreatitis-associated protein (PAP) were performed. The usefulness of each marker for predicting severity was compared with that of Ranson's score. Time of evolution was considered for improving their usefulness. Seventy-one patients were studied. Severe cases had higher levels of all markers, although only IL-10 had better accuracy than Ranson's. In patients admitted during the first 48 h, IL-6, IL-10, and PAP had improved accuracy over Ranson's; however, after this time frame, only CRP outperformed Ranson's score. Analysis of time frames improved the accuracy of all markers. Therefore, time of evolution should be considered when using these parameters for a better prognosis.
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PMID:Time frames for analysis of inflammatory mediators in acute pancreatitis: improving admission triage. 1908 18

Acute lung injury is one of the critical complications of acute pancreatitis (AP). Tumor necrosis factor-associated factor 6 (TRAF6) is a key adaptor that regulates various inflammatory signaling pathways, including those mediated by Toll-like receptors (TLRs). This study was performed to investigate the potential role of TRAF6 in the pathogenesis of AP and pancreatitis-associated acute lung injury using a mouse model of caerulein-induced AP (CAP). CAP was induced by intraperitoneal injection of caerulein hourly for 7 times (50 microg/kg), and control mice were treated with saline of the same volume. Typical pancreatic and lung inflammation was observed in the early stage (1 h) of CAP, as judged by morphological changes. Likewise, in CAP mice, the pancreatic myeloperoxidase activity and serum levels of interleukin-6 and interleukin-10 were significantly increased after 2 h, peaked at 4h, and then decreased by 24 h. The expression of TRAF6 was then studied by real time-PCR, immunohistochemistry, and Western blot analysis. Compared with control group, TRAF6 mRNA level was decreased in CAP group within the first 12 h, and then significantly increased after 24 h, which was in accordance with the protein level detected by Western blot analysis and immunohistochemistry. Moreover, TRAF6 protein was expressed in both pancreatic acinar cells and lung bronchial epithelial cells. In conclusion, the down-regulation of TRAF6 was associated with increased inflammatory severity in the pancreas and lung, suggesting that TRAF6 is involved in the anti-inflammatory process during AP. TRAF6 may be a potential molecular target for treating AP.
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PMID:Down-regulation of tumor necrosis factor-associated factor 6 is associated with progression of acute pancreatitis complicating lung injury in mice. 1934 32

The past few years have witnessed a tremendous progress in our knowledge regarding the pathogenesis, diagnosis, prognostic evaluation and classification of acute pancreatitis. The role of ischemia, lysosomal enzymes, oxygen free radicals, polymorphnuclear cells-byproducts and inflammatory mediators in the pathogenesis of pancreatic necrosis and multiple organ failure has been emphasized. Furthermore, the recent knowledge about agents infecting pancreatic necrosis, routes of infection, bacteriological examination of fine needle aspirate and appropriate antibiotics have changed the concept of acute pancreatitis. New diagnostic tests such as rapid urinary trypsinogen-2 test and inflammatory mediators including polymorphnuclear elastase, C-reactive protein and interleukin-6 contribute to early diagnosis, prognostic evaluation and initiation of an appropriate therapy.
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PMID:Acute pancreatitis. 1986 87


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