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)

Inter-alpha-trypsin inhibitor-4 (Itih-4) is a liver-restricted member of the serine protease inhibitor family with diverse functions as an anti-apoptotic and matrix stabilizing molecule that are important throughout development. We investigate the functional role of Itih-4 in liver formation, regeneration (LR) and examine its role in calcium and hyaluronic acid binding. Itih-4 expression is prominent in early liver development at E9 and later at E16, being restricted to hepatoblasts, immature hepatocytes, and differentiated hepatocytes. We note a marked and differential increase in Itih-4 labeling in proliferating hepatocytes, compared with bile duct cells in liver explant cultures treated with interleukin-6 (IL-6). After partial hepatectomy, maximal Itih-4 expression occurs in a bimodal manner at 30 min and at 12 hr, with a predominant centrizonal distribution. There is no detectable binding of glutathione transferase-fusion Itih-4 protein to calcium and hyaluronic acid, indicating a possible requirement for posttranslational modifications for these functions. These results suggest that in LR, Itih-4 expression corresponds to that of immediate early genes and may contribute to the entry of normally quiescent hepatocytes into the early stages of the cell cycle. The markedly high expression of Itih-4 in early liver development and in explants treated with IL-6 suggests a prominent role for Itih-4 at key points in liver formation.
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PMID:Itih-4, a serine protease inhibitor regulated in interleukin-6-dependent liver formation: role in liver development and regeneration. 1180 70

The underlying mechanisms responsible for both cartilage loss and subchondral bone changes in osteoarthritis (OA) remain unknown. It is becoming recognized that the extracellular matrix influences the metabolism of cells both in vivo and in vitro and can modify their responses to external stimuli. Indeed, the glycosaminoglycan/proteoglycan matrix is of major importance for the proliferation and/or differentiation of a number of cells. Here, we determined the potential role of hyaluronic acid (HA) of increasing molecular weight (MW) to alter the expression of metabolic markers and cytokine production by human osteoarthritic (OA) subchondral osteoblasts (Ob). Both 1,25(OH)(2)D(3)-induced alkaline phosphatase activity (ALPase) and osteocalcin release were increased in OA Ob when compared to normal. HA reduced osteocalcin release in OA Ob at MW of 300 and above, whereas HA failed to significantly modify ALPase. Parathyroid hormone (PTH) stimulated cyclic AMP (cAMP) formation by OA Ob. HA had a biphasic effect on this PTH-dependent activity, totally inhibiting cAMP formation at MW of 300 and 800. HA of increasing MW progressively reduced the levels of Prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6) produced by OA Ob. Interestingly, urokinase plasminogen activator (uPA) and and PA inhibitor-1 (PAI-1) levels were not significantly affected by HA of increasing MW; however, the PAI-1 to uPA ratio showed a slight, yet nonsignificant increase. Surprisingly, uPA activity was increased in OA Ob under the same conditions. Last, HA had no effect on the production of insulin-like growth factor-1 by these cells. Our data suggest that high MW HA can modify cellular parameters in OA Ob that are increased when compared to normal. The effect of HA on inflammatory mediators, such as PGE(2) and IL-6, and on uPA activity is more striking at higher MW as well. Taken together, these results could suggest that HA of increasing MW has positive effects on OA Ob by modifying their biological synthetic capacities.
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PMID:Hyaluronic acid reverses the abnormal synthetic activity of human osteoarthritic subchondral bone osteoblasts. 1455 76

The fate of hematopoietic stem cells (HSCs) is determined by microenvironmental niches, but the molecular structure of these local networks is not yet completely characterized. Our recent observation that glycosaminoglycan hyaluronic acid (HA), a major component of the bone marrow extracellular matrix, is required for in vitro hematopoiesis led us to suggest a role for HA in structuring the hematopoietic niche. Accordingly, HA deprivation induced by various treatments might lead to an imbalance of normal HSC homeostasis. Since 5-fluorouracil (5-FU) administration sharply decreases the amount of cell surface-associated HA in bone marrow, we examined whether the administration of exogenous HA enhances suppressed hematopoiesis in 5-FU-treated mice. HA administered to mice following 5-FU infusion facilitated the recovery of leukocytes and thrombocytes in the peripheral blood. Intravenously infused HA was found in the bone marrow, where it bound endothelial cells and resident macrophages and increased expression of the hematopoiesis-supportive cytokines interleukin-1 and interleukin-6. In agreement with these observations, enhanced hematopoietic activity was detected in the bone marrow, as measured by elevated counts of long-term culture-initiating cells (LTC-ICs), committed progenitors, and the total number of mature bone marrow cells. Overall, our results suggest that HA is required for regulation of the hematopoiesis-supportive function of bone marrow accessory cells and, therefore, participates in hematopoietic niche assembly.
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PMID:Hyaluronic acid facilitates the recovery of hematopoiesis following 5-fluorouracil administration. 1527

An autopsy case of granulocyte colony-stimulating factor (G-CSF)- and interleukin-6 (IL-6)-producing diffuse deciduoid peritoneal mesothelioma is reported. The patient was a 70-year-old man with abdominal distension and weight loss in the year prior to his death. Laboratory data suggested severe inflammation with marked leukocytosis, thrombocytosis and elevated serum levels of C-reactive protein, G-CSF and IL-6. Imaging studies showed an expansive mass occupying the entire abdomen and pelvic cavity. Histological diagnosis of tissue taken by needle biopsy was difficult due to the unusual sarcomatoid-appearance of the tumor. In addition, there was severe infiltration of numerous neutrophilic leukocytes. An autopsy revealed that the diffuse peritoneal tumor had a fresh fishmeat-like appearance with focal mucinous degeneration and entirely encased the abdominal organs. Histological examination showed a sheet-like proliferation of tumor cells with large ovoid or polygonal cytoplasm, large atypical nuclei and obvious nucleoli. The tumor cells showed abundant glycogen and hyaluronic acid, and were immunoreactive to cytokeratin, calretinin, epithelial membrane antigen (EMA), CA-125, and focally to vimentin. The tumor cells were immunoreactive to G-CSF and IL-6. Electron microscopy revealed long, slender microvilli on the tumor cell surface. This tumor was diagnosed as a G-CSF- and IL-6-producing, diffuse deciduoid mesothelioma. We report this case with special reference to the differential diagnosis of deciduoid peritoneal mesothelioma with paraneoplastic syndrome.
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PMID:Granulocyte-colony stimulating factor- and interleukin 6-producing diffuse deciduoid peritoneal mesothelioma. 1530 18

The removal of low molecular weight proteins such as beta(2)-microglobulin (beta(2)MG) is accelerated by using a 7.5% icodextrin-based peritoneal dialysis solution (ICO) dwell. To examine the possibility of peritoneal injury in ICO, we investigated the relationship between beta(2)MG and the injury markers in effluent. Sixteen ICO-treated patients (11 male and five female, mean age 50.1 +/- 10.9 years) with continuous ambulatory peritoneal dialysis (CAPD; mean duration 54.6 +/- 30.8 months) were studied. The patients were treated with ICO 2 L and 2.27% glucose-based solution 2 L for an 8-h dwell and the effluent was collected. We investigated the correlations between beta(2)MG and the injury markers (e.g. hyaluronic acid [HA], interleukin-6 [IL-6], matrix metalloproteinase-2 [MMP-2]) in each effluent sample. The beta(2)MG level in the ICO effluent was 8978 +/- 2431 microg/L, significantly higher than in the 2.27% glucose-based solution effluent (6454 +/- 2956 microg/L; P = 0.0032). The levels of HA and MMP-2 in ICO effluent were significantly higher than those in the 2.27% glucose-based solution effluent (P = 0.00214, P = 0.0113, respectively). There was a trend toward higher IL-6-values in ICO effluent, although no significant differences were seen. There were positive correlations between levels of various injury markers and beta(2)MG. We propose that the subclinical injury of the peritoneum by ICO treatment may accelerate peritoneal permeability to increase beta(2)MG in effluent. ICO's biocompatibility might not be superior to that of glucose-based solution.
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PMID:Relationship between effluent levels of beta(2)-microglobulin and peritoneal injury markers in 7.5% icodextrin-based peritoneal dialysis solution. 1766 36

Urinary interleukin-6 (IL-6) has been proposed as a sensitive and specific inflammatory marker in bladder pain syndrome/interstitial cystitis (BPS/IC). We therefore investigated the presence of urinary IL-6 in patients with BPS/IC to find a possible correlation with the symptoms before and after glycosaminoglycan substitution therapy. Urinary IL-6 levels of 25 BPS/IC patients were assessed semi-quantitavely (Milenia Quickline) before and after intra-vesical glycosaminoglycan substitution therapy. Patients received therapy twice weekly with 300 mg pentosanpolysulphate for 5 weeks. Responders were treated for another 5 weeks, whilst non-responders received 40 mg hyaluronic acid weekly for another 10 weeks instead. Treatment response was assessed by the visual analogue scale (VAS) for quality of life and O'Leary-Saint Symptom and Problem Index (OSPI) before, during the 5th week of the treatment and 1 week after the treatment. Before treatment, measurable IL-6 was found in urine samples from 9 out of 25 patients. After treatment, urinary IL-6 was detected in two patients only. The average VAS and OSPI scores before the treatment were 7.9 (4-10) and 25.4 (12-37), respectively. After the treatment, the average VAS and OSPI scores dropped to 5.5 (0-10) and 14.7 (1-29), respectively. No statistically significant difference was found between patients with and without urinary IL-6 and the VAS and OSPI scores before and after the treatment. The urinary IL-6 level in BPS/IC patients is neither suited as a diagnostic marker nor as a predictor of responses to therapies. For the future, it would be important to clarify whether there are subsets of patients with diseases of different aetiologies.
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PMID:Is there a relation between urinary interleukin-6 levels and symptoms before and after intra-vesical glycosaminoglycan substitution therapy in patients with bladder pain syndrome/interstitial cystitis? 1798 9

To investigate the effect of taurine on alcoholic liver disease in rats, male Wistar rats were administered alcohol intragastrically for 3 months. The effect of beta-alanine-mediated taurine depletion and taurine administration on the development of alcoholic liver disease was examined. It was found that taurine administration produced lower levels of aspartate aminotransferase and alkaline aminotransferase than that of the untreated group. In addition, the levels of hepatic total protein, glutathione and superoxide dismutase were higher in the taurine treated groups than those in the untreated control or the taurine depleted groups, while hepatic malondialdehyde content exhibited the negative effect. Moreover, the concentrations of hepatic hydroxyproline, serum hyaluronic acid, interleukin-2, interleukin-6, tumor necrosis factor-alpha and laminin were all decreased in the taurine treated groups. The pathological changes showed that the percentage of fatty degeneration and inflammation in the taurine groups were lower than that of the control, taurine depleted and automatic recovery groups. These in vivo findings demonstrate that hepatic disease caused by chronic alcohol consumption can be prevented and cured by administration of taurine.
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PMID:Effect of taurine on alcoholic liver disease in rats. 1850 91

To investigate the effect of taurine on alcoholic liver disease in rats, male Wistar rats were administered alcohol intragastrically for 3 months. The effect of beta-alanine-mediated taurine depletion and taurine administration on the development of alcoholic liver disease was examined. It was found that taurine administration produced lower levels of aspartate aminotransferase and alkaline aminotransferase than that of the untreated group. In addition, the levels of hepatic total protein, glutathione and superoxide dismutase were higher in the taurine treated groups than in the untreated control or the taurine depleted group, while hepatic malondialdehyde content exhibited the opposite effect. Moreover, the content of hepatic hydroxyproline, serum hyaluronic acid, interleukin-2, interleukin-6, tumor necrosis factor-alpha and laminin were all decreased in the taurine treated group. The pathological changes showed that the percentage of fatty degeneration and inflammation in the taurine group were less than that of the control, taurine depleted and automatic recovery groups. These in-vivo findings demonstrate that hepatic disease caused by chronic alcohol consumption can be prevented and reversed by administration of taurine.
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PMID:Effect of taurine on alcoholic liver disease in rats. 1923 62

Fibroblasts play a key role in tissue healing by producing the majority of extracellular matrix components, favouring granulation tissue formation, and stimulating re-epithelialization. Hyaluronan is a component of ECM and its anti-inflammatory effects and properties in enhancing wound closure are well known. In this study, we examined the effects of Aminogam gel, a new pharmacological preparation suggested to improve wound healing, composed of hyaluronic acid, proline, lysine, glycine and leucine, on human fibroblasts. Results show that fibroblasts treated with hyaluronic acid plus aminoacid solution increased their proliferative activity, collagen I and III, and fibronectin synthesis. Moreover, HA plus aminoacid solution increased the expression of transforming growth factor beta, connective tissue growth factor, interleukin-6 and -8, assayed by RT-PCR. These results suggested that Aminogam gel, involved in several stages of wound healing, as fibroblast proliferation, granulation tissue formation, ECM component deposition, and production of cytokines, may be a useful device to favour and accelerate wound closure.
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PMID:Enhancement of fibroblast proliferation, collagen biosynthesis and production of growth factors as a result of combining sodium hyaluronate and aminoacids. 1950

The fact whether Blastocystis hominis can invade has always been in question. Apart from a few sporadic studies such as that done on gnotobiotic guinea pigs which showed surface invasion and mucosal inflammation of the host's intestine caused by B. hominis infection, no real documentation of invasion has been proven. Studies have shown that hyaluronidase is secreted during the penetration into the host's skin and gut by nematode parasites. Hyaluronidase activity in protozoa namely Entamoeba histolytica has also been described previously. This study attempts to determine hyaluronidase in urine samples of B. hominis-infected rats. The presence of hyaluronidase in urine provides an indirect evidence of invasion by B. hominis into colonic epithelium causing the degradation of extracellular matrix proteins namely hyaluronic acid (HA). HA is depolymerized by hyaluronidase which may be used by organisms to invade one another. In this study, the levels of urinary hyaluronidase of Sprague-Dawley rats infected with B. hominis were monitored for 30 days. Hyaluronidase levels in the infected rats were significantly higher on days 28 and 30 compared to the day before inoculation (P < 0.01 and P < 0.05, respectively). During this stage, parasitic burden in infected stools was also at a high level. Proinflammatory cytokines, interleukin-6 and interleukin-8, were also significantly higher (P < 0.05) in the serum of infected rats. The study demonstrates that since no other pathogen was present and that amoeboid forms of the parasites have been shown to exist previously, the elevated levels of hyaluronidase in this preliminary finding suggests that the organism is capable of having invasion or penetration activity in the hosts' intestine.
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PMID:Urinary hyaluronidase activity in rats infected with Blastocystis hominis--evidence for invasion? 2035 28


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