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)

The native GroEL-like protein was purified from Campylobacter rectus, a putative periodontal pathogen, by affinity chromatography on ATP-agarose followed by high performance liquid chromatography on Superose 6. The purified 64-kDa protein (denatured form of GroEL-like protein) was immunoreactive by SDS-PAGE and Western immunoblotting with the monoclonal antibody directed against heat shock protein 60 of human origin. The native GroEL-like protein stimulated both interleukin-6 (IL-6) and IL-8 secretion by a confluent monolayer of human gingival fibroblast in their culture supernatant. During the 22-h incubation, the amounts of IL-6 and IL-8 were increased by 5.4- and 3.5-fold, respectively. These data suggested that the GroEL-like protein might be considered to be a virulence factor of C. rectus in periodontal disease.
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PMID:The GroEL-like protein from Campylobacter rectus: immunological characterization and interleukin-6 and -8 induction in human gingival fibroblast. 978 45

The sympathetic nervous system innervates immune organs and, when activated, releases its signaling molecules in the vicinity of immune cells. The released molecules include the "classical" transmitters norepinephrine and epinephrine and the co-transmitters ATP and adenosine. Immune cells express various adrenergic and purinergic receptors that are sensitive to these molecules, and the production of immune/inflammatory mediators (cytokines, chemokines, and free radicals) is modulated by activation of these receptors. Notably, the production of tumor necrosis factor-alpha, interleukin-6, -10, and -12, and the chemokine macrophage inflammatory protein 1alpha and the production of the free radical nitric oxide, produced by the inducible nitric oxide synthase, have been shown to be altered by activation of these receptors. Alterations in the production of the immune mediators may contribute to the development of various diseases. On the other hand, novel experimental therapies based on the modulation of adrenergic or purinergic receptors on immune cells are emerging. Such approaches may have beneficial effects in limiting tissue injury and suppressing symptoms in certain pathophysiological states.
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PMID:Regulation of cytokine and chemokine production by transmitters and co-transmitters of the autonomic nervous system. 980 16

The effects of glutamate (Glu) and ATP on interleukin-6 (IL-6) production from cultured neonatal rat astrocyte were studied. Glu (100-200 mumol.L-1) strongly increased, IL-6 production at 16 h in a dose-dependent manner and ATP (50-100 mumol.L-1) induced a inhibition effect. The results suggest that Glu stimulted IL-6 release may be one of mechanisms of astrocyte "neuroprotective" function in ischmia/reperfusion.
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PMID:[Effects of glutamate and ATP on interleukin 6 production by cultured neonatal rat astrocyte]. 986 50

In the thymus, sympathetic nerves run in septa in close connection to subcapsular/perivascular thymic epithelial cells (TEC). Since TEC are supposed to create a microenvironment of cytokines necessary for the development of thymocytes to T cells, we investigated the influence of sympathetic transmitters and co-transmitters on interleukin-6 (IL-6) synthesis in cultivated rat TEC that express markers of perivascular/subcapsular TEC. Noradrenaline and ATP stimulated IL-6 production in the culture supernatants 14- and 23-fold over basal values after 24 h. Co-stimulation with noradrenaline and ATP yielded an additive effect. Synthesis of IL-6 was concentration-dependent upon ATP and appeared to be mediated by P2 purinoceptors. During 24 h stimulation with 1 mM ATP, two thirds of the ligand was degraded mainly to ADP, production of AMP and adenosine was minor or negligible. Thus, in TEC, transmitters and co-transmitters of the sympathetic nervous system have a co-stimulatory effect on synthesis of IL-6 that is an important factor for thymocyte differentiation and proliferation.
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PMID:Effect of transmitters and co-transmitters of the sympathetic nervous system on interleukin-6 synthesis in thymic epithelial cells. 987 34

Progressive weight loss is a common feature of many types of cancer and is responsible not only for a poor quality of life and poor response to chemotherapy, but also a shorter survival time than is found in patients with comparable tumors without weight loss. Although anorexia is common, a decreased food intake alone is unable to account for the changes in body composition seen in cancer patients, and increasing nutrient intake is unable to reverse the wasting syndrome. Although energy expenditure is increased in some patients, cachexia can occur even with a normal energy expenditure. Various factors have been investigated as mediators of tissue wasting in cachexia. These include cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma) and leukemia inhibitory factor (LIF), as well as tumor-derived factors such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF), which can directly mobilize fatty acids and amino acids from adipose tissue and skeletal muscle respectively. Induction of lipolysis by the cytokines is thought to result from an inhibition of lipoprotein lipase (LPL), although clinical studies provide no evidence for an inhibition of LPL in the adipose tissue of cancer patients. Instead there is an increased expression of hormone sensitive lipase, the enzyme activated by LMF. Protein degradation in cachexia is associated with an increased activity of the ATP-ubiquitin-proteasome pathway. The biological activity of both the LMF and PMF was shown to be attenuated by eicosapentaenoic acid (EPA). Clinical studies show that this polyunsaturated fatty acid is able to stabilize the rate of weight loss and adipose tissue and muscle mass in cachectic patients with unresectable pancreatic cancer. Knowledge of the mechanism of cancer cachexia should lead to the development of new therapeutic agents.
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PMID:Wasting in cancer. 991 7

The aim of the current article is to overview the recent developments in the field of hemorrhagic shock research, as it relates to the roles of nitric oxide (NO) in the pathogenesis of this condition. The first part of the review focuses on the roles of peroxynitrite, a reactive oxidant produced from the reaction of NO and superoxide. The second part of the review deals with the novel findings related to the recently identified regulatory roles of the inducible isoform of nitric oxide synthase (iNOS) in the expression of pro-inflammatory mediators in hemorrhagic shock. (1) The role of peroxynitrite: Immunohistochemical and biochemical evidence demonstrate the production of peroxynitrite in hemorrhagic shock. Peroxynitrite can initiate a wide range of toxic oxidative reactions. These include initiation of tyrosine nitration, lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane sodium/potassium ATP-ase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of hemorrhagic shock. A combined anti-inflammatory agent, mercaptoethylguanidine, which selectively inhibits iNOS and scavenges peroxynitrite, prevents the delayed vascular decompensation and the cellular energetic failure associated with late hemorrhagic shock. Peroxynitrite is a potent trigger of DNA single strand breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Pharmacological inhibition of PARS, with 3-aminobenzamide or 5-iodo-6-amino-1,2-benzopyrone, improves hemodynamic status and prolongs survival time in rodent and porcine models of severe hemorrhagic shock. (2) Novel signaling roles of induced NO in hemorrhagic shock. Although the severity and duration of shock may dictate the timing and extent of iNOS expression, it is now evident that the up-regulation of iNOS can take place during sustained shock. Accumulated data indicate that iNOS expressed during shock contributes to vascular decompensation, as classically described by Wiggers. In addition, the presence of even low levels of iNOS at the time of resuscitation enhances the inflammatory response that follows the reperfusion state. Pharmacological inhibition of iNOS with N6-(iminoethyl)-L-lysine or genetic inactivation of iNOS (iNOS knockout mice) attenuates the activation of the transcription factors nuclear factor kappa B (NFkappaB) and Signal Transducer and Activator of Transcription 3 (STAT3), and ameliorates the increases in interleukin-6 and G-CSF messenger RNA levels in the lungs and liver. Inhibition of iNOS results in a marked reduction of lung and liver injury produced by hemorrhagic shock. Thus, induced nitric oxide, in addition to being a "final common mediator" of hemorrhagic shock, is essential for the up-regulation of the inflammatory response in resuscitated hemorrhagic shock. Furthermore, a picture of a pathway is evolving that contributes to tissue damage both directly via the formation of peroxynitrite, with its associated toxicities, and indirectly through the amplification of the inflammatory response.
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PMID:Novel roles of nitric oxide in hemorrhagic shock. 1046 45

An immortal nonhormone-producing cell line with a characteristic star-shaped morphology, named Tpit/F1, was derived from an anterior pituitary gland of a temperature-sensitive large T antigen transgenic mouse. To characterize Tpit/F1 cells, we performed cytological studies, which revealed that Tpit/F1 cells express the messenger RNAs of neruonal nitric oxide (NO) synthase, S-100 protein, basic fibroblast growth factor, and pituitary-restricted transcription factor. The Tpit/F1 cells response to pituitary adenylate cyclase-activating peptide comprised the stimulated secretion of interleukin-6. Furthermore, glucocorticoids stimulate glutamine synthase production by Tpit/F1 cells. Considering these cytological characteristics together with their morphology, we deduced that Tpit/F1 cells are derived from pituitary folliculo-stellate (FS) cells. Our cytophysiological analyses of Tpit/F1 cells revealed that intracellular Ca2+ increased dose dependently on ATP administration (0-100 microM), and that this effect did not require the presence of extracellular Ca2+ and was not abolished by treatment with gadolinium, a Ca2+ channel blocker. The ATP-induced increase in intracellular Ca2+ ([Ca2+]i) was completely abolished by treatment with the Ca2+-adenosine triphosphatase (Ca2+-ATPase) inhibitor thapsigargin, which suggests that ATP increases [Ca2+]i by mobilizing internally stored Ca2+ followed by an influx of Ca2+. Moreover, UTP was equipotent with ATP in causing the [Ca2+]i increase in Tpit/F1 cells. Also, the Ca2+ response was prevented by the phospholipase C inhibitor, U-73122, but not by its inactive analog, U-73343. From these results we therefore concluded that ATP acts on Tpit/F1 cells via P2Y2-purinoceptors. Interestingly, both neuronal nitric oxide synthase messenger RNA and NO secretion were increased by ATP administration (10 and 100 microM). These results suggest the biological significance of the topological colocalization of FS cells and endocrine cells. Namely, ATP is cosecreted with hormones from endocrine cells and stimulates NO production by FS cells, and the released NO may regulate neighboring endocrine cell and blood vessels.
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PMID:Cytological characterization of a pituitary folliculo-stellate-like cell line, Tpit/F1, with special reference to adenosine triphosphate-mediated neuronal nitric oxide synthase expression and nitric oxide secretion. 1101 14

Establishment of salivary cell lines retaining normal morphological and physiological characteristics is important in the investigation of salivary cell function. A submandibular gland cell line, SMG-C6, has recently been established. In the present study, we characterized the phosphoinositide (PI)-Ca2+ signaling system in this cell line. Inositol 1,4,5-trisphosphate(1,4,5-IP3) formation, as well as Ca2+ storage, release, and influx in response to muscarinic, alpha1-adrenergic, P2Y-nucleotide, and cytokine receptor agonists were determined. Ca2+ release from intracellular stores was strongly stimulated by acetylcholine (ACh) and ATP, but not by norepinephrine (NA), epidermal growth factor (EGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha). Consistently, 1, 4,5-IP3 formation was dramatically stimulated by ACh and ATP. ACh-stimulated cytosolic free Ca2+ concentration [Ca2+]i increase was inhibited by ryanodine, suggesting that the Ca2+-induced Ca2+ release mechanism is involved in the ACh-elicited Ca2+ release process. Furthermore, ACh and ATP partially discharged the IP3-sensitive Ca2+ store, and a subsequent exposure to thapsigargin (TG) induced further [Ca2+]i increase. However, exposure to TG depleted the store and a subsequent stimulation with ACh or ATP did not induce further [Ca2+]i increase, suggesting that ACh and ATP discharge the same storage site sensitive to TG. As in freshly isolated submandibular acinar cells, exposure to ionomycin and monensin following ACh or TG induced further [Ca2+]i increase, suggesting that IP3-insensitive stores exist in SMG-C6 cells. Ca2+ influx was activated by ACh, ATP, or TG, and was significantly inhibited by La3+, suggesting the involvement of store-operated Ca2+ entry (SOCE) pathway. These results indicate that in SMG-C6 cells: (i) Ca2+ release is triggered by muscarinic and P2Y-nucleotide receptor agonists through formation of IP3; (ii) both the IP3-sensitive and -insensitive Ca2+ stores are present; and (iii) Ca2+ influx is mediated by the store-operated Ca2+ entry pathway. We conclude that Ca2+ regulation in SMG-C6 cells is similar to that in freshly isolated SMG acinar cells; therefore, this cell line represents an excellent SMG cell model in terms of intracellular Ca2+ signaling.
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PMID:Characterization of the calcium signaling system in the submandibular cell line SMG-C6. 1108 16

Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.
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PMID:Loss of skeletal muscle in cancer: biochemical mechanisms. 1117 57

Enlarged fat cells exhibit modified metabolic capacities, which could be involved in the metabolic complications of obesity at the whole body level. We show here that sterol regulatory element-binding protein 2 (SREBP-2) and its target genes are induced in the adipose tissue of several models of rodent obesity, suggesting cholesterol imbalance in enlarged adipocytes. Within a particular fat pad, larger adipocytes have reduced membrane cholesterol concentrations compared with smaller fat cells, demonstrating that altered cholesterol distribution is characteristic of adipocyte hypertrophy per se. We show that treatment with methyl-beta-cyclodextrin, which mimics the membrane cholesterol reduction of hypertrophied adipocytes, induces insulin resistance. We also produced cholesterol depletion by mevastatin treatment, which activates SREBP-2 and its target genes. The analysis of 40 adipocyte genes showed that the response to cholesterol depletion implicated genes involved in cholesterol traffic (caveolin 2, scavenger receptor BI, and ATP binding cassette 1 genes) but also adipocyte-derived secretion products (tumor necrosis factor alpha, angiotensinogen, and interleukin-6) and proteins involved in energy metabolism (fatty acid synthase, GLUT 4, and UCP3). These data demonstrate that altering cholesterol balance profoundly modifies adipocyte metabolism in a way resembling that seen in hypertrophied fat cells from obese rodents or humans. This is the first evidence that intracellular cholesterol might serve as a link between fat cell size and adipocyte metabolic activity.
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PMID:Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes. 1127 95


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