UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines have been implicated as immunological effector molecules that induce dysfunction and destruction of the pancreatic beta-cell. The mechanisms of cytokine action on the beta-cell are unknown; however, nitric oxide, resulting from cytokine-induced expression of nitric oxide synthase, has been implicated as the cellular effector molecule mediating beta-cell dysfunction. Nitric oxide is a free radical that targets intracellular iron-containing enzymes, which results in the loss of their function. The cytokine IL-1 beta induces the formation of nitric oxide in isolated rat islets and the insulinoma cell line, Rin-m5F. NMMA and NAME, both inhibitors of nitric oxide synthase, completely protect islets from the deleterious effects of IL-1 beta. These inhibitors are competitive in nature and inhibit both the cytokine-inducible and constitutive isoforms of nitric oxide synthase with nearly identical kinetics. This may preclude their use as therapeutic agents because of increases in blood pressure which result from the inhibition of constitutive nitric oxide synthase activity. Aminoguanidine, an inhibitor of nonenzymatic glycosylation of cellular and extracellular constituents associated with diabetic complications, recently has been reported to inhibit nitric oxide synthase. Aminoguanidine is approximately 40-fold more effective in inhibiting the inducible isoform of nitric oxide synthase, suggesting that aminoguanidine or analogues may serve as potential therapeutic agents to block diseases associated with nitric oxide production by the inducible isoform of nitric oxide synthase. In vivo administration of TNF IL-1 has been shown to induce anti-diabetogenic effects in the NOD mouse. This anti-diabetogenic effect of cytokines appears to conflict with evidence suggesting that cytokines mediate beta-cell dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Does nitric oxide mediate autoimmune destruction of beta-cells? Possible therapeutic interventions in IDDM. 137 15

To assess whether nitric oxide (NO) formed by IL-1 beta affects vasopressin (AVP) and atrial natriuretic hormone (ANH) release and the regulation of blood pressure and body temperature, intravenous infusion of either N omega-nitro-L-arginine methyl ester (L-NAME) alone (50 micrograms/kg.body weight.min for 135 min), human recombinant interleukin 1 beta (IL-1 beta) alone (750 ng/kg.body weight.min for 120 min), or L-NAME (50 micrograms/kg.body weight.min for 135 min) with IL-1 beta (750 ng/kg.body weight.min for 120 min), was performed following priming doses of L-NAME (2 mg/kg.body weight) and IL-1 beta (7.5 micrograms/kg.body weight) into conscious rats (n = 6 each). In the control group, saline alone was administered. Plasma AVP and ANH, mean arterial blood pressure (MABP), heart rate (HR) and rectal temperature (RT) were determined. In response to L-NAME, plasma AVP significantly increased, but plasma ANH did not change, despite increases in MABP and decreases in HR. In response to IL-1 beta, both plasma AVP and ANH increased with decreases in MABP and RT without any changes in HR. With L-NAME and IL-1 beta, both plasma AVP and ANH increased, and depressor response to IL-1 beta was partly attenuated by L-NAME, without any changes in RT. With saline alone, none of these parameters changed during the study. These results suggest that NO may directly affect the release of AVP and ANH and the regulation of body temperature and blood pressure, but NO formed by IL-1 beta may not have direct effects on the release of these hormones, and the regulation of blood pressure and temperature.
...
PMID:Effects of a nitric oxide synthase inhibitor on vasopressin and atrial natriuretic hormone release, thermogenesis and cardiovascular functions in response to interleukin-1 beta in rats. 753 27

1. Myocardial dysfunction during septic shock is associated with enhanced production of cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). These cytokines depress cardiac mechanical function by a mechanism which is not well defined. 2. Bacterial endotoxin or cytokines cause the expression of Ca(2+)-independent nitric oxide (NO) synthase in cardiac myocytes, vascular endothelial cells and endocardial endothelial cells, causing enhanced production of NO. As NO has negative inotropic actions on cardiac muscle, we tested the sum effects of IL-1 beta plus TNF-alpha in the intact heart to determine whether enhanced expression of NO synthase activity in the cells that comprise the heart is involved in cardiac depression associated with cytokine stimulation. 3. Rat isolated working hearts perfused with IL-1 beta plus TNF-alpha showed a markedly greater depression in contractile function, measured as cardiac work, after 2 h of perfusion compared with time-matched control hearts. The depressant action of IL-1 beta plus TNF-alpha was first apparent after 1 h of perfusion; no early (15 min) cardiac depressant actions were seen. 4. The competitive inhibitor of Ca(2+)-dependent and Ca(2+)-independent NO synthases, NG-nitro-L-arginine methyl ester (L-NAME, 3 microM) when given concurrently with IL-1 beta plus TNF-alpha prevented the loss in contractile function such that these hearts after 2 h of perfusion had similar function to time-matched controls. L-NAME did not acutely reverse the loss of contractile function in hearts exposed for 2 h to IL-1 beta plus TNF-alpha. The protective action of L-NAME in the presence of cytokines was concentration-dependent and was not seen at a higher concentration (10 micro M) due to the significant reduction in coronary flow observed at this concentration.5. In contrast, when L-NAME (3 micro M) was given in the absence of IL-l beta plus TNF-alpha it depressed contractile function over the 2 h perfusion period by significantly reducing coronary flow.6. Inhibition of protein synthesis with cycloheximide (Cx) abolished the loss in function that occurred over 2h in both control and IL-1 beta plus TNF-a-treated hearts.7. Inducible, Ca2+-independent NO synthase activity was not observed in freshly isolated hearts but was observed in control hearts perfused for 2 h in vitro and was doubled in hearts perfused with IL-1 beta plus TNF-a. Cx prevented the expression of Ca2+-independent NO synthase in both control and cytokine-treated hearts.8. In summary, these results suggest that the depression of myocardial function by IL-l beta plus TNF-alpha is mediated, at least in part, by induction of Ca2+-independent NO synthase activity in the heart.
...
PMID:The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. 753 96

The effect of cytokines, growth factors, mitogens, and bacterial products on nitric oxide (NO) generation by monolayers of small intestinal epithelial cells-6 (IEC-6) cells was evaluated. Subconfluent IEC-6 cells were maintained in DMEM containing 5% fetal calf serum and after 16-24 hr of incubation, the medium was replaced with fresh medium in the presence or absence of calcium ionophore (CaI), L-NAME, L-NNA, individual growth factors, cytokines, or mitogens. After 72 hr of culture, the media supernatant was collected and NO chi generation was determined. NO synthase activity was determined in sonicated supernatants of IEC-6 cells by [14C] arginine conversion to citrulline. NO chi generation in subconfluent cultures was greater than in fully confluent cultures, suggesting contact inhibition. NO chi generation by IEC-6 cells was significantly increased by CaI and inhibited by L-NAME and L-NNA. LPS, IL-1 beta, IL-2, IL-8, IFN-8, TFN-alpha, EGF, TGF-alpha, bFGF, and PHA significantly increased NO chi generation. NO synthase activity in IEC-6 cells (4.2 +/- 1.7 pmol/min/10(6) cells) was NADPH dependent. These results suggest that stimulation of NO chi generation by intestinal epithelial cells through cytokine bacterial products and mitogens may be one of the mechanisms responsible for their effects in the intestinal tract.
...
PMID:NO chi generation by cultured small intestinal epithelial cells. 755 34

Blockade of nitric oxide (NO) formation with the arginine derivative L-N omega nitro-L-arginine-methylester (L-NAME) produces a dramatic increase in ACTH released by the iv injection of interleukin-1 beta (IL-1 beta). The present work investigated the potential role of three mechanisms in this effect: the activation of adrenergic receptors and/or the release of vasopressin (VP) or prostaglandins (PG). As previously observed, blockade of adrenergic receptors with prazosin and propranolol did not alter the stimulatory effect of IL-1 beta. We show here that this treatment did not significantly interfere with the potentiating influence of L-NAME 30 min after IL-1 injection, but blunted this effect at 60 min. Immunoneutralization of endogenous VP did not consistently decrease the ACTH response to IL-1 beta regardless of whether NO was present. Finally, as expected, blockade of PG synthesis with ibuprofen totally abolished IL-1 beta-induced ACTH secretion; in addition, it prevented the interaction between L-NAME and the pituitary response. In contrast to results obtained after the injection of IL-1 beta, neither the adrenergic antagonists nor ibuprofen significantly altered the ability of L-NAME to potentiate the stimulatory effect of VP. Collectively, these results indicate that the influence of NO on ACTH released by blood-borne IL-1 beta (an effect thought to be primarily exerted on nerve terminals in the median eminence) is not primarily mediated by endogenous VP. The inability of L-NAME to augment the stimulatory effect of the cytokine on ACTH secretion in the presence of ibuprofen suggests that PG play an obligatory role in the response of the hypothalamic-pituitary axis to systemic cytokine administration that cannot be compensated for by removing the restraining influence of NO. Finally, removal of the inhibitory effect of NO either unmasks the participation of adrenergic receptors in modulating the response of the hypothalamic-pituitary axis to IL-1 beta or stimulates catecholamine secretion, which, in turn, acts on CRF nerve terminals and/or synergizes with IL-1 beta-induced CRF release.
...
PMID:Blockade of nitric oxide formation augments adrenocorticotropin released by blood-borne interleukin-1 beta: role of vasopressin, prostaglandins, and alpha 1-adrenergic receptors. 762 98

Administration of Escherichia coli endotoxin abolished the acid secretory response induced by a bolus injection of pentagastrin in the continuously perfused stomach of the anaesthetized rat. Likewise, acid secretion stimulated by the continuous intravenous perfusion of pentagastrin was inhibited by administration of interleukin-1 beta (IL-1 beta). In both cases pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) but not dexamethasone or indomethacin substantially restored the secretory responses to pentagastrin. The actions of L-NAME were reversed by the prior administration of L-arginine but not by its enantiomer D-arginine. Even though L-NAME increased blood pressure, this does not seem to be the mechanism by which endotoxin-induced acid inhibition was prevented, since similar systemic pressor responses induced by phenylephrine had no such effect. The secretory response elicited by pentagastrin in the isolated lumen perfused stomach of the rat was not influenced by incubation (100 min) with IL-1 beta. These observations suggest that the acute inhibition of acid responses to pentagastrin by endotoxin and IL-1 beta involves nitric oxide (NO) synthesis from L-arginine.
...
PMID:Involvement of endogenous nitric oxide in the inhibition by endotoxin and interleukin-1 beta of gastric acid secretion. 788 Oct 19

To characterize the L-arginine/nitric oxide (NO) pathway in human vascular smooth muscle (VSM), contractile responses of isolated internal mammary arteries (IMA) and saphenous veins (SV) were observed after induction of NO synthase by interleukin-1 beta (IL-1 beta) or by lipopolysaccharide (LPS). In IL-1 beta-treated endothelium-denuded rings, contractile responses to phenylephrine were reduced in SV rings only. Maximum phenylephrine-induced contraction was depressed by approximately 50%. This was not modified by the presence of indomethacin, NG-nitro-L-arginine methyl ester (L-NAME), or methylene blue (MeB). In LPS-treated vessels, contractile responses were depressed in both SV and IMA rings (40%), and this was not affected by indomethacin. In SV, L-NAME, NG-monomethyl-L-arginine, or MeB did not affect the inhibitory effect of LPS, whereas the effect was reversed in IMA by these inhibitors. In LPS-treated IMA, but not in SV, exogenous L-arginine evoked significant vasodilation (20%). We conclude that VSM of the human IMA possesses an L-arginine/NO pathway inducible by LPS. In SV, LPS or IL-1 beta treatment inhibits contraction by an unidentified system that is not dependent on NO synthase or on guanylate cyclase activities.
...
PMID:Inducible L-arginine/nitric oxide pathway in human internal mammary artery and saphenous vein. 790 Aug 66

Gamma interferon (IFN-gamma) and interleukin(IL)-1 beta produced by T lymphocytes and macrophages may have significant roles in the airway inflammation seen in bronchial asthma and are known to modify functions of both immune and non-immune cells. In this study, we examined whether the cytokines can modify contractile and relaxing responses of guinea pig airway strips in vitro. The isometric tension of guinea-pig strips was measured in a tissue bath filled with Krebs-Henseleit solution. Contracting responses to carbachol and KCl, and the relaxing response to isoproterenol (ISO) were examined. Effects of the cytokines were examined by comparing responses of the strips incubated with or without IFN-gamma (1,000 U/ml, 25,000 U/ml) and IL-1 beta (25 ng/ml, 250 ng/ml). Contracting responses to carbachol and KCl were not affected by the incubation with IFN-gamma but slightly increased in maximum contraction by carbachol after 5 hours incubation with 25,000 U/ml of IFN-gamma. Both 1- and 5-hour incubation of the strips with 250 ng/ml of IL-1 beta significantly decreased the sensitivity to KCl without affecting maximum contraction. 1- and 5-hour incubation of the strips with 25,000 U/ml of IFN-gamma or 250 ng/ml of IL-1 beta significantly increased or decreased the sensitivity to ISO without affecting maximum relaxation, respectively. Denudation of epithelium from the strips completely abolished the effects of the cytokines on KCl and ISO responses. In addition, the effects of IFN-gamma on ISO relaxation and IL-1 beta on KCl contraction were abolished by indomethacin but not by N omega-nitro-L-arginine methyl ester (N omega-NAME). The effect of IL-1 beta on ISO was inhibited both by indomethacin and by N omega-NAME. These results suggest that IFN-gamma and IL-1 beta may modify airway smooth muscle responses through their effects on airway epithelium by inducing the release of prostanoids and/or nitric oxide.
...
PMID:[Effects of gamma interferon (IFN-gamma) and interleukin-1 beta (IL-1 beta) on contractile and relaxing responses of guinea-pig airway strips]. 792 71

Nitric oxide (NO) synthase (NOS), the enzyme responsible for NO formation, is found in hypothalamic neurons containing oxytocin (OT), vasopressin (VP), and to a lesser extent corticotropin-releasing factor (CRF). Because NO is reported to modulate endocrine activity, we have investigated the hypothesis that endogenous NO participates in ACTH released by various secretagogues in the rat. In the adult male rat, the intravenous injection of interleukin-1 beta (IL-1 beta; 0.2-0.3 micrograms/kg), VP (0.3-0.9 micrograms/kg), and OT (30 micrograms/kg) significantly increased plasma ACTH and corticosterone levels. Pretreatment with the L-form, but not the D-form, of N omega nitro-L-arginine-methylester (L-NAME; a specific inhibitor of NOS) markedly augmented the effects of these secretagogues whether it was injected acutely or over a 4 d period. Blockade of NOS activity also caused significant (P < 0.01) extensions of the duration of action of IL-1 beta, VP, and OT. In contrast, L-NAME did not significantly alter the stimulatory action of peripherally injected CRF, or centrally administered IL-1 beta. Administration of L-arginine, but not D-arginine (100 mg/kg), used as a substrate for basal NO synthesis and which did not by itself alter the activity of the hypothalamic-pituitary-adrenal (HPA) axis, blunted IL-1-induced ACTH secretion, and reversed the interaction between L-NAME and IL-1 beta. The stimulatory action of endotoxin, a lipopolysaccharide that releases endogenous cytokines, was also augmented by inhibition of NO formation.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:In the rat, endogenous nitric oxide modulates the response of the hypothalamic-pituitary-adrenal axis to interleukin-1 beta, vasopressin, and oxytocin. 815 53

Release of inflammatory mediators by mast cells can be modulated by certain cytokines and by nitric oxide. An in vitro platelet aggregation bioassay was used to assess the effects of interleukin-1 beta (IL-1 beta) on the release of platelet-activating factor and nitric oxide from resting or ionophore-activated peritoneal mast cells (PMC) from rat. PMC spontaneously released a substance that inhibits thrombin-stimulated platelet aggregation. The activity of this substance is abolished by addition of hemoglobin to the platelet suspension and augmented by preincubation of the PMC with L-arginine, suggesting that it is nitric oxide. Within minutes, IL-1 beta concentration-dependently (1 pg/ml-100 ng/ml) enhanced the release from activated PMC of nitric oxide, as measured by its ability to inhibit thrombin-induced platelet aggregation, and as confirmed with a biochemical assay for nitrite. This action of IL-1 beta was inhibited by pretreatment of PMC with a calmodulin antagonist (calmidazolium), an IL-1 receptor antagonist, or either of two nitric oxide synthase inhibitors (L-NAME and LY-83583). IL-1 beta also inhibited the release of platelet-activating factor from PMC through a nitric-oxide-dependent mechanism. These results demonstrate that IL-1 beta is a potent and rapid-acting modulator of mast cell reactivity, stimulating nitric oxide release while inhibiting the production of platelet-activating factor.
...
PMID:Modulation of rat mast cell reactivity by IL-1 beta. Divergent effects on nitric oxide and platelet-activating factor release. 839 60

1 2 3 Next >>