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

Restoration of blood flow to an acutely ischemic lower limb may, paradoxically, result in systemic complications and unexpected mortality. We investigated the effect of acute ischemia-perfusion of the lower limb on cytokine production and end organ function. Plasma concentrations of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were determined in five groups of male Wistar rats: control, 3 hours of bilateral hind limb ischemia alone, and 3 hours of bilateral hind limb ischemia followed by 1 hour, 2 hours, or 3 hours of reperfusion, respectively. In a second experiment, the effect of lower limb ischemia-reperfusion on remote organs (lung, liver, and kidney) was assessed biochemically and histologically. There was a significant increase in plasma concentrations of TNF-a in plasma of animals subjected to 3 hours of bilateral hind limb ischemia followed by 1 hour of reperfusion, 40.1 +/- 4.4 pg/ml, when compared with controls, 22.6 +/- 4.4 pg/ml, or animals in the ischemia-alone group, 16.3 +/- 5.2 (p <0.05). Plasma concentration of IL-6 increased progressively and significantly in animals subjected to bilateral hind limb ischemia followed by 1 hour of reperfusion, 720 +/- 107 pg/ml; 2 hours of reperfusion, 1987 +/- 489 pg/ml; or 3 hours of reperfusion, 6284 +/- 1244 (p <0.0001), compared with controls, 104 +/- 43 pg/ml; or animals in the ischemia-alone group, 140 +/- 55 pg/ml. In the study comparing portal and systemic concentrations of IL-6, systemic concentrations of IL-6, 967 +/- 184 pg/ml were significantly higher than those in the portal circulation 577 +/- 127 pg/ml (p <0.05). There was a significant increase in plasma concentrations of urea, creatinine, aspartate transaminase, alanine transaminase, and lactic dehydrogenase in reperfused animals compared with controls (p <0.001). Morbidity and mortality following reperfusion of the acutely ischemic limb may be a manifestation of multiple organ dysfunction caused by a systemic inflammatory response triggered by reperfusion of the ischemic extremities.
 ...
PMID:Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction. 1502 26

The prevalence of respiratory allergies has increased over the last 20 years, highlighting the need for a simple and noninvasive tool to investigate, in a clinical and epidemiological context, airway-inflammation mechanisms encountered in allergic and inflammatory processes. The nose, as the first region of the respiratory tract to come in contact with airborne pollutants, is easily explored with the use of nasal lavage (NL). We evaluated an NL method for adults and children, along with its reproducibility and capacity to separate different subgroups. NL reproducibility, assessed in 10 healthy, nonsmoking adults on three different occasions, was determined with the use of the intraclass coefficient of correlation for such inflammatory markers as total cell count, albumin, urea, neutrophil elastase, alpha(1)-antitrypsin, interleukin-6, and interleukin-8. Using this NL method, we analyzed nasal markers of 50 healthy adults (smokers and nonsmokers) and 12 healthy children. Our NL method demonstrated high reproducibility with regard to total cell count, albumin, urea, and alpha(1)-antitrypsin (intraclass correlation coefficient > 0.75). Compared with NL results in nonsmokers, NL in heavy smokers revealed significant increased concentrations of total cell counts and interleukin-8 and significant decreased concentrations of interleukin-6. These findings suggest that NL can be used as a tool in the assessment of inflammation because it has the correct reproducibility and can discriminate between heavy smokers and nonsmokers. Moreover, the use of this standardized method in children is feasible.
 ...
PMID:Nasal lavage as a tool for the assessment of upper-airway inflammation in adults and children. 1194 28

Engineered tissues provide an opportunity to investigate important physiological processes difficult to study in whole perfused organs and animal models. For example, a hepatocyte culture model consisting of rat hepatocytes cultured in a collagen sandwich configuration, which exhibits stable differentiated liver-specific functions, may be useful to investigate liver pathophysiology. To investigate systemic inflammation-related hepatic failure, we chronically exposed hepatocytes to the inflammatory mediators interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) for up to 4 weeks. IL-6 (2.5 ng/mL) transiently suppressed albumin (-90%) and chronically increased fibrinogen (+6-fold) production. IL-6 inhibited urea synthesis at 2.5 ng/mL and stimulated it at 0.025 ng/mL. IL-1beta (10 ng/mL) inhibited albumin (-90%), urea (-40 to 50%), and IL-6-stimulated fibrinogen (-90%) secretion. The inhibitory effect of IL-1beta on urea secretion was dose-dependent. Furthermore, IL-1beta transiently stimulated nitric oxide (NO) synthesis; however, NO did not mediate the effect of IL-1beta on albumin and fibrinogen production, and played a minor role in IL-1beta-mediated urea synthesis suppression. In conclusion, IL-1beta and IL-6 exert, via a direct effect on hepatocytes, long-term inhibitory effects on hepatic functions that are potentially important for the survival of the host, which may contribute to hepatic dysfunction in prolonged inflammatory states.
 ...
PMID:Long-term stable cultures of rat hepatocytes: an in vitro model to study acute and chronic hepatic inflammation. 1220 7

Most prior studies have characterized hepatocyte proliferative responses in culture systems that do not express a stable differentiated phenotype. We investigated the DNA synthetic response of long-term stable hepatocyte cultures to growth factor stimulation as well as conditioning with nonparenchymal cells (NPCs). Primary rat hepatocytes were cultured on a single layer of collagen (h/C) or Matrigel (h/M), or in a collagen sandwich (C/h/C) or collagen-Matrigel sandwich (M/h/C). Hepatocytes were cultured for 7 days to allow phenotypic stabilization before growth factor addition, except for h/C cultures, which are unstable, where growth factors were added 1 day after seeding. Culture medium was supplemented with a mixture of hepatocyte, epidermal, and vascular endothelial growth factors and interleukin-6, either directly or after conditioning with NPCs for 24 h. Growth factors alone induced hepatocyte DNA synthesis, as measured via [3H]thymidine uptake, in the h/C, C/h/C, and M/h/C configurations. h/M exhibited very low levels of DNA synthesis. In the C/h/C and M/h/C configurations, the greatest stimulation was obtained using NPC-conditioned growth factors. This response was sustained for several days and without decreasing albumin or urea synthesis. These results suggest that hepatocyte mitogens and NPC-derived factors can stimulate DNA synthesis in stable and differentiated hepatocyte cultures.
 ...
PMID:Growth factors and nonparenchymal cell conditioned media induce mitogenic responses in stable long-term adult rat hepatocyte cultures. 1472 61

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this. In an ex vivo model of human blood, PepG containing different amino acids induced similar levels of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10, whereas muramidase digestion nearly abolished the ability to induce cytokine release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG. However, additional experiments showed that muramidase-treated PepG synergized with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood, despite its lack of inflammatory activity when administered alone. Based on these studies, we hypothesize that the structural integrity of the glycan chain of the PepG molecule is very important for the pathogenic effects of PepG. The amino acid composition of PepG, however, does not seem to be essential for the inflammatory properties of the molecule.
 ...
PMID:Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain. 1497 33

Surgery remains the only curative treatment option for cholangiocarcinoma (CC). Currently, both early identification of CC in affected individuals at high risk and accurate diagnosis of unexplained biliary strictures are problematic. However, growing insights into biochemical and molecular mechanisms underlying biliary carcinogenesis have suggested serum and bile markers for the diagnosis of CC. These tools include tumor antigens or products (e.g., carbohydrate antigen [CA] 19-9), cytokines (e.g., interleukin-6), metabolic products (e.g., lactate), proteases (e.g., trypsinogen-2), regulatory peptides (e.g., pancreatic polypeptide), and (epi-)genetic lesions (e.g., K- ras and p53 mutations, p16 (INK4a) or p14 (ARF) promoter hypermethylation). In this article we discuss these new potential tumor markers for the diagnosis of CC.
 ...
PMID:Serum and bile markers for cholangiocarcinoma. 1519 87

Porcine interleukin-6 (PIL-6) protein without signal peptide was expressed as a glutathione S-transferase (GST) fusion protein in Escherichia coli. The fusion protein was expressed in an insoluble fraction, however, it was solubilized by refolding procedure using urea. From the solubilized protein, the recombinant PIL-6 (rPIL-6) was purified by a batch method using glutathione sepharose 4B and PreScission protease cleavage. By the B3B1 hybridoma cell proliferation assay, biological activity of the purified rPIL-6 was confirmed. Three monoclonal antibodies (MAbs) named 2B-1, 5A-8 and 4C-3 were generated by using the rPIL-6 as an immunogen. Immunoglobulin isotypes of the MAbs were IgG2a (4C-3) and IgG2b (2B-1 and 5A-8). For the epitope analysis, additive enzyme-linked immunosorbent assay and immunoblot analysis using deletion mutants of PIL-6 were performed. These experiments revealed that the two MAbs (2B-1 and 5A-8) recognize an overlapped epitope and the other (4C-3) recognizes a distinct epitope, and all epitopes reside in the region of aa26-64 of PIL-6.
 ...
PMID:Generation of monoclonal antibodies to porcine interleukin 6 (PIL-6) using the recombinant PIL-6 expressed in Escherichia coli. 1547 67

Bioartificial liver support systems have demonstrated limited efficacy in compensation of liver detoxification and substitution of liver-derived factors. However, in these devices, the biological substitution of the complex liver function has been restricted to xenogeneic or transformed hepatocytes. Therefore, we have examined the long-term effect of coculturing normal human hepatocytes (HCs) with allogeneic biliary epithelial cells (BECs). We applied functional in vitro assays to examine their metabolic potential by ammonia detoxification to urea, cytochrome P450-dependent lignocaine conversion to mono-ethyl-glycine-xylidide (MEGX), and protein expression and secretion. As the liver has a pivotal role in the synthesis of coagulation factors, we measured antithrombin III (AT III), factor VII, and albumin, comparing HCs plated on collagen or inside 3-dimensional collagen gels. Over 30 days, expression and secretion of albumin and clotting factors by human HCs were augmented by culture inside collagen gel, but were also enhanced and better maintained by coculture with BECs. Higher proportions of BECs cocultured with HCs substantially increased the protein synthesis and urea production. Remarkably, the almost absent cytochrome P450 activity of HC alone after 1 week could be reversed and maintained over 3 weeks by coculture with BECs. The pattern of these effects differed from the extent of interleukin-6 (IL-6) production and HC viability under the compared conditions. In conclusion, coculture of human HCs with BECs impressively restores the synthetic and metabolic liver function in vitro. These results suggest mechanisms of improved liver epithelial differentiation supported by coculture conditions. This technique offers new perspectives in bioartificial liver support, hepatocyte transplantation, and stem cell differentiation.
 ...
PMID:Preservation of the synthetic and metabolic capacity of isolated human hepatocytes by coculture with human biliary epithelial cells. 1577 38

The aim of this study was to investigate the influence of N-acetylcysteine (NAC) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increase in mortality rate, pancreatic necrosis and serum activity of amylase, alanine aspartate transferase (ALT), interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and significant decrease of concentrations of calcium, blood pressure, urine output and pO(2). The use of NAC inhibited the changes in urine output, pO(2), tissue activity of MPO and MDA in pancreas and lungs, and the serum activity of IL-6, ALT, and serum concentrations of urea and calcium. NAC reduced the mortality and pancreatic damage. The use of NAC has a beneficial effect on the course of ANP in rats. It may be used in the treatment of acute pancreatitis.
 ...
PMID:Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats. 1608 83

To clarify the laboratory characteristics and deduce the pathogenesis of acute encephalopathy associated with multiple organ dysfunctions in Japan. We measured cytokine levels [tumor necrosis factor alpha (TNF-alpha), soluble tumor necrosis factor-receptor 1 (sTNF-R1), and interleukin-6 (IL-6)] in serum and cerebrospinal fluid (CSF) as well as general laboratory examinations in 27 patients with acute encephalopathy. Urea nitrogen (UN), creatinine (Cr), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and C-reactive protein (CRP) levels in blood, and CSF protein levels at the initial stage were significantly higher in patients with an unfavorable outcome. TNF-alpha, sTNF-R1, and IL-6 levels at the initial stage were higher in the serum than in the CSF of patients with acute encephalopathy. Serum cytokine levels correlated well with patient outcome. The high CSF protein level and the high UN, Cr, AST, LDH, and CRP levels in the blood represent the severity of vascular leakage through the blood-brain barrier and multiple organ dysfunctions, respectively, and thus suggest an unfavorable prognosis. The high serum inflammatory cytokine levels at the initial stage and the good correlation of those levels with the outcome suggest that intravascular inflammation has a significant role in vascular leakage and multiple organ dysfunctions in acute encephalopathy.
 ...
PMID:Laboratory characteristics of acute encephalopathy with multiple organ dysfunctions. 1619 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>