Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory stimuli and lipid peroxidation activate nuclear factor kappa B (NF-kappaB) and upregulate proinflammatory cytokines and chemokines. The present study evaluated the relationship between pathological liver injury, endotoxemia, lipid peroxidation, and NF-kappaB activation and imbalance between pro- and anti-inflammatory cytokines. Rats (5 per group) were fed ethanol and a diet containing saturated fat, palm oil, corn oil, or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. Pathological analysis was performed and measurements of endotoxin were taken, lipid peroxidation, NF-kappaB, and messenger RNA (mRNA) levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNFalpha], interleukin-1 beta [IL-1beta], interferon-gamma, [IFN-gamma], and IL-12), C-C chemokines (regulated upon activation, normal T cell expressed and secreted [RANTES], monocyte chemotactic protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha), C-X-C chemokines (cytokine induced neutrophil chemoattractant (CINC), MIP-2, IP-10, and epithelial neutrophil activating protein [ENA]-78), and anti-inflammatory cytokines (IL-10, IL-4, and IL-13). Activation of NF-kappaB and increased expression of proinflammatory cytokines C-C and C-X-C chemokines was seen in the rats exhibiting necroinflammatory injury (fish oil-ethanol [FE] and corn oil-ethanol[CE]). These groups also had the highest levels of endotoxin and lipid peroxidation. Levels of IL-10 and IL-4 mRNA were lower in the group exhibiting inflammatory liver injury. Thus, activation of NF-kappaB occurs in the presence of proinflammatory stimuli and results in increased expression of proinflammatory cytokines and chemokines. The Kupffer cell is probably the major cell type showing activation of NF-kappaB although the contribution of endothelial cells and hepatocytes cannot be excluded. Downregulation of anti-inflammatory cytokines may additionally exacerbate liver injury.
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PMID:Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat. 1049 45

Hepatic ischemia/reperfusion injury is initiated by the activation of Kupffer cells and their subsequent release of proinflammatory mediators, including tumor necrosis factor-alpha (TNFalpha). These mediators stimulate a cascade of events including up-regulation of CXC chemokines and vascular endothelial adhesion molecules, leading to hepatic neutrophil recruitment and tissue injury. Interleukin-13 (IL-13) is a cytokine that has been shown to suppress macrophage production of proinflammatory mediators. The objective of the current study was to determine whether IL-13 could regulate the liver inflammatory injury induced by ischemia and reperfusion. C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by reperfusion with or without intravenous administration of recombinant murine IL-13. Hepatic ischemia/reperfusion increased expression of TNFalpha and macrophage inflammatory protein-2 (MIP-2), leading to hepatic neutrophil recruitment, hepatocellular injury, and liver edema. Administration of IL-13 reduced the production of TNFalpha and MIP-2 mRNA and protein. IL-13 suppressed liver neutrophil recruitment by up to 72% and hepatocellular injury and liver edema were each reduced by >60%. Administration of IL-13 had no effect on liver NFkappaB activation, but greatly increased the activation of STAT6. The data suggest that the hepatoprotective effects of IL-13 may be a result of STAT6 activation.
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PMID:IL-13 activates STAT6 and inhibits liver injury induced by ischemia/reperfusion. 1051 88

Lung tissue may be an important source of systemic inflammation associated with sepsis and the acute respiratory distress syndrome (ARDS). An ex vivo model of freshly explanted lung tissue in culture was developed to evaluate the ability of lipopolysaccharide (LPS) to directly stimulate lung tissues under conditions where indirect mechanisms such as recruitment of blood-derived inflammatory cells could not be implicated. Under control conditions, lung explants produced a high level of macrophage inflammatory protein-2 (MIP-2). Eight hours after LPS challenge, there were marked increases in the production of tumor necrosis factor-alpha (TNF-alpha) from 0.18 +/- 0.04 to 4.13 +/- 0.23 ng/ml/g tissue (p < 0.05), MIP-2 from 60.0 +/- 7.4 to 165.6 +/- 10.3 ng/ml/g tissue (p < 0.05), and tissue lipid peroxidation (malonaldehyde from 27.6 +/- 2.5 to 48.4 +/- 17.5 microM/g tissue; and 4-hydroxyalkenal from 34.0 +/- 3.0 to 59.7 +/- 18.8 microM/g tissue, both p < 0.05) from lung explants. Treatment with the beta-adrenoreceptor agonist isoproterenol (1 ng/ml) attenuated LPS-induced release of TNF-alpha and lipid peroxidation in association with an increase in intracellular cAMP levels. The adenylate cyclase activator, forskolin, also inhibited LPS-induced changes in TNF-alpha and lipid peroxidation. In conclusion, increasing intracellular levels of cAMP through beta-adrenoreceptor activation can attenuate the acute inflammatory response induced in the lung by LPS. LPS did not significantly impair the beta-adrenoreceptor reactivity in lung explants. Lung explants allow for the quantitative assessment of pulmonary inflammatory responses independent of influences from the circulation, and thus may be a useful ex vivo model to investigate cellular and molecular mechanisms of lung injury.
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PMID:Effect of adrenoreceptors on endotoxin-induced cytokines and lipid peroxidation in lung explants. 1055 44

Hepatic ischemia and reperfusion cause local and remote organ injury. This injury culminates from an integrated cascade of proinflammatory cytokines, chemokines, and adhesion molecules, many of which are regulated by the transcription factor nuclear factor-kappaB (NF-kappaB). The anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to have inhibitory effects on NF-kappaB. The objective of the current study was to determine whether IL-10 could suppress pulmonary NF-kappaB activation and ensuing lung injury induced by hepatic ischemia-reperfusion. C57BL/6 mice underwent partial hepatic ischemia with or without intravenous administration of IL-10. Hepatic ischemia-reperfusion resulted in pulmonary NF-kappaB activation, increased mRNA expression of tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2), as well as increased pulmonary neutrophil accumulation and lung edema. Administration of IL-10 suppressed lung NF-kappaB activation, reduced TNF-alpha and MIP-2 mRNA expression, and decreased pulmonary neutrophil recruitment and lung injury. The data suggest that IL-10 protects against hepatic ischemia and reperfusion-induced lung injury by inhibiting lung NF-kappaB activation and the resulting pulmonary production of proinflammatory mediators.
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PMID:Interleukin-10 inhibits pulmonary NF-kappaB activation and lung injury induced by hepatic ischemia-reperfusion. 1056 76

The interaction of air particles and alveolar macrophages (AMs) may result in the release of proinflammatory cytokines. Normal mouse AMs were treated with concentrated air particle (CAPs) suspensions in vitro. After 5 h, cytokine release [macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-alpha)] and phagocytosis of ambient air particles were measured. CAPs samples collected from urban air (Boston) on different days were used. The CAPs samples and their soluble and solid components caused significant MIP-2 and TNF-alpha production. Variability in the potency of samples collected on different days was observed. Trace endotoxin was measured in CAPs samples (EU/mg: 2.3 +/- 0.7, mean +/- SE, n = 10). A majority of biologic activity (cytokine induction) and endotoxin content was associated with the solid components. Neutralization of endotoxin by polymyxin B abrogated >80% of TNF-alpha induction by CAPs samples, but inhibited MIP-2 production by only approximately 40%. The trace endotoxin present in CAPs caused much more MIP-2 production than predicted by concentration alone (28 +/- 8-fold increase, n = 9), indicating synergistic interaction with other AM-activating components of the particles. Data suggest that low levels of endotoxin may interact with air particles to activate lung macrophages.
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PMID:Alveolar macrophage cytokine production in response to air particles in vitro: role of endotoxin. 1066 32

Macrophage inflammatory protein-2 (MIP-2) belongs to the C-X-C subfamily of chemokines and appears to play an important role in cytokine-induced inflammatory and immune cell-mediated responses. We found that tumor necrosis factor-alpha (TNF-alpha) time- and dose-dependently increased gene and protein expression of MIP-2 in endothelial cells. Moreover, it was observed that dexamethasone treatment inhibited endothelial cell expression of MIP-2 in response to TNF-alpha stimulation and markedly reduced the number of adherent neutrophils. Moreover, we found that a monoclonal antibody against murine MIP-2 abolished neutrophil adhesion to TNF-alpha-activated endothelial cells. These data demonstrate that TNF-alpha induces expression of MIP-2 in endothelial cells and support the hypothesis that the anti-inflammatory action of dexamethasone may, at least in part, be attributable to an inhibition of MIP-2 induction on cytokine-activated endothelial cells.
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PMID:Dexamethasone inhibits tumor necrosis factor-alpha-induced expression of macrophage inflammatory protein-2 and adhesion of neutrophils to endothelial cells. 1079 3

An external evaluation program for measuring the performance of laboratories testing for cytokines and immune activation markers in biological fluids was developed. Cytokines, chemokines, soluble cytokine receptors, and other soluble markers of immune activation (CSM) were measured in plasma from a healthy human immunodeficiency virus (HIV)-seronegative reference population and from HIV-seropositive individuals as well as in supernatant fluids from in vitro-stimulated human immune cells. The 14 components measured were tumor necrosis factor (TNF) alpha, gamma interferon, interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, Rantes, MIP-Ia, MIP-Ibeta, soluble TNF receptor II, soluble IL-2 receptor alpha, beta(2)-microglobulin, and neopterin. Twelve laboratories associated with the Adult and Pediatric AIDS Clinical Trial Groups participated in the study. The performance features that were evaluated included intralaboratory variability, interlaboratory variability, comparison of reagent sources, and ability to detect CSM in the plasma of normal subjects as well as the changes occurring in disease. The principal findings were as follows: (i) on initial testing, i.e., before participating in the program, laboratories frequently differed markedly in their analytic results; (ii) the quality of testing of a CSM in individual participating laboratories could be assessed; (iii) most commercial kits allowed distinction between normal and abnormal plasma CSM levels and between supernatants of stimulated and unstimulated cells; (iv) different sources of reagents and reference standards frequently provided different absolute values; (v) inexperienced laboratories can benefit from participating in the program; (vi) laboratory performance improved during active participation in the program; and (vii) comparability between analyses conducted at different sites can be ensured by an external proficiency testing program.
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PMID:Need for an external proficiency testing program for cytokines, chemokines, and plasma markers of immune activation. 1088 48

Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.
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PMID:Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury. 1107 4

Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell-mediated autoimmune diseases and delayed-type hypersensitivity reactions (DTHRs) in the skin, joints, and gut, but are absent in T cell-mediated autoimmune diseases of the brain or pancreas. All of these reactions are mediated by interferon gamma-producing type 1 T cells and produce a similar pattern of cytokines. Thus, the cells and mediators responsible for the PMN recruitment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapten-induced DTHRs of the skin, we found that mast cells determine the T cell-dependent PMN recruitment through two mediators, tumor necrosis factor (TNF) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the functional analogue of human interleukin 8. Extractable MIP-2 protein was abundant during DTHRs in and around mast cells of wild-type (WT) mice but absent in mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-)(v) (Kit(W)/Kit(W)(-v)) mice. T cell-dependent PMN recruitment was reduced >60% by anti-MIP-2 antibodies and >80% in mast cell-deficient Kit(W)/Kit(W)(-v) mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2-dependent PMN recruitment in Kit(W)/Kit(W)-(v) mice, whereas mast cells from TNF(-/)- mice did not. Thus, mast cell-derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell-mediated DTHRs.
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PMID:Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. 1108 46

Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific effect of halothane on this response.
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PMID:Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats. 1111 52


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