Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of cytokines directly from cardiac myocytes has not been previously demonstrated and could represent an important mechanism and site of intervention in ischemia and reperfusion injuries. Macrophage inflammatory protein-2 (MIP-2) and monocyte chemotactic protein (MCP) are chemotactic cytokines (chemokines) that stimulate polymorphonuclear leukocytes (PMNs) and monocytes, respectively. Endothelium has been implicated as being a major cellular source of leukocyte-activating factors. We hypothesized that the myocardial cells may also play an important role in producing chemokines independently of endothelium. Primary cultures of adult rat ventricular myocytes were prepared. Cultured myocytes were stimulated with either interleukin 1 (IL-1), tumor necrosis factor (TNF), or lipopolysaccharide (LPS). MIP-2 and MCP mRNA were expressed in adult rat myocytes following stimulation. Our studies indicate that ventricular myocytes expressed chemokine mRNA and protein in both a dose- and time-dependent fashion. MIP-2 and MCP release, determined by enzyme-linked immunosorbent assay, was biologically active, accounting for approximately 40% of the PMN and monocyte chemotactic activity produced by these cells. These results suggest that cardiac myocytes may directly recruit activated leukocytes into areas of injury. Such a recruiting process could underlie the migration of leukocytes into areas of oxidant stress and play a role in development of reperfusion injury of myocardium.
 ...
PMID:Cardiac myocytes release leukocyte-stimulating factors. 757 43

The effect of global ischemia and reperfusion on the expression of cytokine genes and cell adhesion molecules by myocardial tissues and neutrophils was studied by using the Langendorff model. Although cardiac function deteriorated after reperfusion of ischemic hearts, there was no evidence of inflammation and myocardial degeneration, which is in contrast to previous findings that neutrophil-mediated inflammation is a critical step in post-ischemic reperfusion injury in regional ischemia. Flow cytometry analysis demonstrated that the global ischemia and reperfusion did not affect the expression of adhesion molecules on neutrophils. We also examined the expression of various cytokines which are involved in inflammatory responses. Only interleukin 1 alpha was induced after the reperfusion of the ischemic hearts. These results suggest that neutrophils barely contribute to the myocardial dysfunction and IL-1 alpha may play a role in post-ischemic myocardial dysfunction during the early stage of reperfusion.
 ...
PMID:Neutrophil-independent myocardial dysfunction during an early stage of global ischemia and reperfusion of isolated hearts. 762 55

We have previously proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. NO previously has been found to inhibit mitochondrial activity in other cell types. Accordingly, we sought to determine if cytokine-stimulated NO production inhibited cardiac myocyte mitochondrial activity. Treatment of neonatal rat cardiac myocytes with interleukin-beta (IL-1) resulted in the expression of mRNA for inducible NO synthase (iNOS) and stained positively for iNOS protein by immunohistochemistry. No iNOS staining was detected in untreated cells. IL-1 treatment resulted in significant nitrite levels vs control over 48 hrs (4.2 +/- 0.7 vs 0.3 +/- 0.2 nmol/1.25 x 10(5) cells, respectively) (n = 12) that was inhibited by 1mM NMA (0.3 +/- 0.2 nmoles; p < .01; n = 12). Mitochondrial activity was assessed by the MTT colorimetric assay using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and OD 570-630. Mitochondrial activity was significantly inhibited by IL-1 vs control cells (0.436 +/- 0.01 vs 0.608 +/- 0.03) and reversed by 1mM NMA (0.549 +/- 0.03) or removal of IL-1 (0.662 +/- 0.02) (p < .01; n = 12 for each). These data strongly suggest that cytokine-stimulated NO production by cardiac myocytes results in reversible inhibition of mitochondrial activity.
 ...
PMID:Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. 765 17

The cytokine tumor necrosis factor (TNF-alpha) is a pleotrophic polypeptide that plays a significant role in brain immune and inflammatory activities. TNF-alpha is produced in the brain in response to various pathological processes such as infectious agents [e.g., human immunodeficiency virus (HIV) and malaria], ischemia, and trauma. TNF-alpha mRNA is rapidly produced in response to brain ischemia within 1 h, reaches a peak at 6-12 h post ischemia, and subsides 1-2 days later. TNF-alpha mRNA expression corresponds in a temporal fashion to other cytokines such as interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and IL-1 and precedes the infiltration of inflammatory cells into the injured zone. TNF-alpha is present early in neuronal cells in and around the ischemic tissue (penumbra), yet at later time points, the peptide is found in macrophages in the infarcted tissue. TNF-alpha has been demonstrated to cause expression of proadhesive molecules on the endothelium, which results in leukocyte accumulation, adherence, and migration from capillaries into the brain. Furthermore, TNF-alpha activates glial cells, thereby regulating tissue remodeling, gliosis, and scar formation. Thus, evidence is emerging in support of a role for TNF-alpha in injury induced by infectious, immune, toxic, traumatic, and ischemic stimuli. TNF-alpha promotes inflammation by stimulation of capillary endothelial cell proinflammatory responses and thereby provides leukocyte adhesion and infiltration into the ischemic brain. The evidence generated so far suggests that agents that suppress TNF-alpha's production or actions will reduce leukocyte infiltration into ischemic brain regions and thereby diminish the extent of tissue loss.
 ...
PMID:Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha. 788 Jul 18

To elucidate mechanisms underlying neuroprotective properties of astrocytes in brain ischemia, production of neurotrophic mediators was studied in astrocytes exposed to hypoxia/reoxygenation (H/R). Rat astrocytes subjected to H/R released increased amounts of interleukin (IL) 6 in a time-dependent manner, whereas levels of tumor necrosis factor and IL-1 remained undetectable. IL-6 transcripts were induced in hypoxia and the early phase of reoxygenation, whereas synthesis and release of IL-6 antigen/activity occurred during reoxygenation. Elevated levels of IL-6 mRNA were due, at least in part, to increased transcription, as shown by nuclear runoff analysis. The mechanism stimulating synthesis and release of IL-6 antigen by astrocytes was probably production of reactive oxygen intermediates (ROIs), which occurred within 15-20 minutes after placing hypoxia cultures back into normoxia, as the inhibitor diphenyl iodonium inhibited the burst of ROIs and subsequent IL-6 generation (blockade of nitric oxide formation had no effect on ROI generation or IL-6 production). Enhanced IL-6 generation was also observed in human astrocytoma cultures exposed to H/R. Survival of differentiated PC12 cells exposed to H/R was potentiated by conditioned medium from H/R astrocytes, an effect blocked by neutralizing anti-IL-6 antibody. In a gerbil model of brain ischemia, IL-6 activity was lower in the hippocampus, an area sensitive to ischemia, compared with IL-6 activity in the cortex, an area more resistant to ischemia. IL-6 antigen, demonstrated immunohistochemically, was increased in astrocytes from ischemic regions of gerbil brain. These data suggest that H/R enhances transcription of IL-6, resulting in increased translation and release of IL-6 antigen after the burst of ROI generated early during reoxygenation. Release of IL-6 from astrocytes could exert a paracrine neurotrophic effect in brain ischemia.
 ...
PMID:Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival. 796 2

We examined the therapeutic value of an interleukin-1 inhibitor on brain edema formation using a transient focal ischemia model in rats. Rats were given an interleukin-1 blocker, or interleukin-1 release inhibitor immediately after reperfusion. In rats treated with interleukin-1 inhibitor, ischemic brain edema 1 day after reperfusion was significantly decreased compared to that of saline-treated control rats. The simultaneous application of an IL-1 release inhibitor and a lipoxygenase inhibitor showed an additive beneficial effect on brain edema formation. These findings suggest that blocking IL-1 activity ameliorates brain edema and attenuates the neuronal damage induced by focal transient ischemia in rats.
 ...
PMID:Blocking of interleukin-1 activity is a beneficial approach to ischemia brain edema formation. 797 72

Immunological events are implicated in the brain damages after ischemia. Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. We showed beneficial effect of antineutrophol monoclonal antibody RP3, which depletes circulationing neutrophils, on brain edema formation and infarct size. In addition, marked increase in IL-8 concentration was detected in brain and serum during early reperfusion. Time course of IL-8 production precedes brain edema formation and neutrophil infiltration. It is reported that IL-1 induces IL-8 production and anti-IL-1 antibody significantly reduced ischemic brain damages. Neutralizing antibodies against cell adhesion molecules (ICAM-1 and LFA-1) regulate neutrophil: endothel adhesion and monoclonal antibodies against these adhesion molecules reduced the size of infarction. These results indicate that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury.
 ...
PMID:[Ischemia and neuroimmunology--ischemia/reperfusion injury]. 799

The myocardial ischemia and reperfusion injury is caused by the re-introduction of coronary circulation in ischemic myocardial tissues. A number of experiments demonstrate that immunological response such as adherence of neutrophils to endothelial cells play a critical role in reperfusion injury. In this paper, the effect of global ischemia and reperfusion on the expression of cytokine genes by myocardial tissues as well as cell adhesion molecules by neutrophils were studied by using Langendorff model. Cardiac dysfunction and immunological response in 25 min global ischemia at 37.5 degrees C followed by 60 min reperfusion were studied in isolated rat heart perfused with blood supplied from support rat (Langendorff model). Cardiac functions were measured with a left intraventricular balloon. The mean post-experimental reduction of the left ventricular end-systolic pressure were 87.5 +/- 1.6% of pre-experimental level in the control perfusion group and 55.5 +/- 5.8% in the reperfusion group. Immunofluorescence flow cytometry showed that ischemia and reperfusion injury did not affect the expression of adhesion molecules on neutrophils which were isolated from perfused blood samples. Cytokine gene expression was analyzed by direct analysis of mRNA obtained from the blood-perfused, isolated rat heart. The level of expression of the cytokine genes was assessed using semiquantitative reverse transcriptase-polymerase chain reaction (semiquantitative RT-PCR). IL-6, IL-8, IFN-gamma, TNF-alpha were expressed in normal heart tissue at low level and were upregulated following ischemia and reperfusion. IL-1 beta, MCP-1 and IL-1 receptor antagonist were not expressed at detectable level in normal heart but were induced following global ischemia. IL-1 alpha was not expressed at detectable level in normal heart but was induced following reperfusion of the ischemic heart. Histological examination of myocardial tissue from the reperfusion group revealed no evidence of myocardial necrosis. Only a mild interstitial edema as well as weak focal hemorrhage was detected after reperfusion of ischemic hearts. These results suggest that there is a process which causes early stage of post-ischemic myocardial dysfunction without involving myocardial necrosis nor infiltration of inflammatory cells.
 ...
PMID:[Cardiac dysfunction and endogenous cytokines in global ischemia and reperfusion injury]. 811 7

Ischemia followed by reperfusion of the rat hind limb resulted in local evidence of injury, as reflected in increased vascular permeability and hemorrhage in skeletal muscle as well as distant organ injury, as reflected by increased vascular permeability and hemorrhage in lung. These changes were proportional to the duration of reperfusion and were associated with neutrophil accumulation in tissue, as quantitated by myeloperoxidase (MPO) content. There was corresponding evidence of complement depletion and increases in plasma IL-1 and IL-6. On the basis of interventional approaches, limb and lung vascular injury was neutrophil and complement dependent and was attenuated by treatment with antioxidants. Products of L-arginine were involved in the development of vascular injury since antagonists of L-arginine were protective. Based on the use of blocking antibodies, the cytokines TNF alpha and IL-1 were also involved in the development of tissue injury. Finally, both LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) beta 2 integrins were required as well as the endothelial adhesion molecules E-selectin and ICAM-1. Protective interventions were more protective that both local and remote organ injury following ischemia-reperfusion is in lung than in skeletal muscle. There were, in general, parallel effects when tissue protection was related to reduction in MPO content. These data suggest dependent on toxic oxygen and L-arginine products of neutrophils, the accumulation of which can be linked to cytokines (TNF alpha, IL-1), beta 2 integrins and endothelial adhesion molecules.
 ...
PMID:Ischemia-reperfusion injury. 831 38

Myocardial dysfunction following prolonged ischemia and reperfusion is at least partially dependent upon adhesion of neutrophils to myocardial and endothelial cells. Neutrophils are thought to contribute to reperfusion injury by two mechanisms: impairment of the microvasculature by physical obstruction, and secretion of products that damage microvasculature and myocardium. Cytokines have been shown to play several roles in neutrophil aggregation. Interleukin-6 (IL-6), along with IL-1 and tumor necrosis factor-alpha (TNF-alpha), induces the expression of intracellular adhesion molecule-1 (ICAM-1) in myocytes and endothelial cells, respectively. These cytokines also inhibit contractility and nitric oxide release (a vasodilator), and IL-1 and TNF-alpha have been found to reduce adrenergic stimulation of myocardial contractility by reducing intracellular cyclic AMP levels and uncoupling adenylate cyclase from beta receptors. The transforming growth factors, TGF-alpha and TGF-beta, also have a role in reperfusion injury. TGF-alpha reduces endothelial cell release of nitric oxide, while TGF-beta appears to protect against reperfusion injury by reducing plasma TGF-alpha levels, blocking neutrophil adherence, and promoting nitric oxide release. Although cytokines are likely to have important roles in reperfusion injury, their involvement in myocardial stunning is unclear.
 ...
PMID:Cytokines and reperfusion injury. 846 22


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