[Advances in the anti-inflammatory mechanism of glucocorticoids].
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Animals↗
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Results for “INFLAMMATORY MECHANISMS”
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The influence of seminal plasma on ovarian function in pigs--a novel inflammatory mechanism?
Seminal plasma is increasingly recognised as contributing to the reproductive process in roles apart from that of providing nutritive support and transport for spermatozoa. Seminal components elicit inflammatory responses in the female reproductive tract, including altered patterns of cytokine secretion, which have consequences for early embryo development and implantation. This review examines evidence, generated principally in the porcine model, for a more recently recognized role for seminal plasma in regulating the temporal kinetics of ovulation, corpus luteum development and steroid production in the ovary. Molecular mechanisms that operate to facilitate communication via a novel semen-uterine-ovarian axis are postulated. A better understanding of these events may facilitate development of strategies to ensure maximal fertility and reduce embryo mortality in the pig and other polyovular species.
Animals↗
Surgical delay and arachidonic acid metabolites: evidence for an inflammatory mechanism: an experimental study in rats.
In a rat skin flap model, surgical delay produced an increase in the production of arachidonic acid metabolites, with a derangement of the normal equilibrium between PGE2 and PGF2 alpha and a marked increase in the vasoconstrictive substance, thromboxane. During the delay period, there is a gradual decrease in tissue levels toward normal. Subsequent elevation of the delayed flap produces a blunted response in thromboxane production, an increase in PGE2 levels and increased flap survival. Acute elevation of an undelayed flap produced more marked elevation of all metabolites, with prolonged elevation of the vasoconstrictive PGF2 alpha and thromboxane, progressive ischemia and decreased flap survival. A key role in inflammation, mediated by these inflammatory mediators, is postulated in the mechanism of delay.
Animals↗
Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f.
Extracts of Tripterygium wilfordii hook. f. (leigong teng, Thundergod vine) are effective in traditional Chinese medicine for treatment of immune inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. Characterisation of the terpenoids present in extracts of Tripterygium identified triptolide, a diterpenoid triepoxide, as responsible for most of the immunosuppressive, anti-inflammatory and antiproliferative effects observed in vitro. Triptolide inhibits lymphocyte activation and T-cell expression of interleukin-2 at the level of transcription. In all cell types examined, triptolide inhibits nuclear factor-kappaB transcriptional activation at a unique step in the nucleus after binding to DNA. Further characterisation of the molecular mechanisms of triptolide action will serve to elucidate pathways of immune system regulation.
Animals↗
Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide.
There is now abundant evidence that brain microglia, when activated, have the lineage, receptors, and synthetic capacity to participate in both potentially neurotoxic inflammatory responses and potentially beneficial phagocytic responses. Amyloid beta peptide (Abeta) forms highly insoluble, beta-pleated aggregates that are widely deposited in the Alzheimer's disease (AD) cortex and limbic system. Aggregated Abeta also activates the classical and alternative complement cascades. These properties make Abeta an excellent target for microglial phagocytosis, a view supported by multiple reports, through well established mechanisms of phagocyte clearance.
Alzheimer Disease↗
Cellular and humoral defense systems and inflammatory mechanisms in thermal injury.
Despite substantial improvements in modern burn care, sepsis is still a common feature in patients with severe thermal injury. Alterations in cell-mediated immunity, changes in inflammatory mediators and neutrophil functions, and recent data obtained from experimental studies in thermal injury are described.
Animals↗
Direct anti-inflammatory mechanisms contribute to attenuation of experimental allograft arteriosclerosis by statins.
BACKGROUND: Despite the development of effective immunosuppressive therapy, transplant graft arterial disease (GAD) remains the major limitation to long-term graft survival. The interplay between host inflammatory cells and donor vascular wall cells results in an intimal hyperplastic lesion, which leads to ischemia and graft failure. HMG-CoA reductase inhibitors (statins) reduce GAD in human cardiac allografts, although it is unclear whether this is secondary to cholesterol lowering or other mechanisms. This study tested the hypothesis that statins can suppress GAD by cholesterol-independent pathways. METHODS AND RESULTS: We performed heterotopic murine cardiac transplants in total allogeneic or major histocompatibility complex class II-mismatched combinations. Transplanted animals received either control chow, chow containing 25 ppm cerivastatin (low dose), or chow containing 125 ppm cerivastatin (high dose). Mean plasma cerivastatin concentrations were 0.0 (control), 10.1 (low dose), and 21.9 (high dose) nmol/L, respectively. Plasma cholesterol levels were the same in all groups. GAD scores decreased in low-dose (P<0.05) and high-dose (P<0.0001) cerivastatin groups compared with controls, with concomitant reduction in graft-infiltrating cells and significantly decreased intragraft RANTES and monocyte chemotactic protein-1 mRNA expression. Cerivastatin, as well as other statins, also reduced RANTES and monocyte chemotactic protein-1 production in mouse endothelial cells stimulated with interferon-gamma and tumor necrosis factor-alpha in vitro. CONCLUSIONS: Clinically achievable levels of an HMG-CoA reductase inhibitor attenuate GAD in murine heart transplants, diminish host inflammatory cell recruitment, and do not alter cholesterol levels. These results indicate that statins can affect arterial biology and inflammation independently of their effects on cholesterol metabolism.
Animals↗
Inflammatory mechanisms in chronic sinusitis.
Apart from ventilatory and bacteriologic aspects, understanding the pathomechanisms of inflammation in chronic sinusitis and nasal polyposis seems crucial for further success in disease treatment. New insights into inflammatory processes became recently possible by investigating the pattern of cytokines and chemokines as well as adhesion molecules in different acute and chronic sinus diseases. The proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and especially the neutrophil-chemoattractant IL-8 play a dominant role in acute sinusitis, as was shown before for viral and allergic rhinitis. In contrast, IL-3 protein dominates the cytokine profile in chronic sinusitis, giving support to a variety of inflammatory cells. The most striking finding was the increased synthesis of IL-5 protein in bilateral nasal polyposis, whereas IL-5 was not found in controls or antrochoanal polyps. As this cytokine is known to enhance eosinophil activation and survival, our data point to IL-5 as a key protein in the pathomechanism of tissue eosinophilia in nasal polyposis. The investigation of cytokine patterns may furthermore help to differentiate between sinusitis subgroups, e.g. in the classification of sinus diseases.
Acute Disease↗
beta-amyloid activates the O-2 forming NADPH oxidase in microglia, monocytes, and neutrophils. A possible inflammatory mechanism of neuronal damage in Alzheimer's disease.
The deposition of beta-amyloid in the brain is the key pathogenetic event in Alzheimer's disease. Among the various mechanisms proposed to explain the neurotoxicity of beta-amyloid deposits, a new one, recently identified in our and other laboratories, suggests that beta-amyloid is indirectly neurotoxic by activating microglia to produce toxic inflammatory mediators such as cytokines, nitric oxide, and oxygen free radicals. Three findings presented here support this mechanism, showing that beta-amyloid peptides (25-35), (1-39), and (1-42) activated the classical NADPH oxidase in rat primary culture of microglial cells and human phagocytes: 1) The exposure of the cells to beta-amyloid peptides stimulates the production of reactive oxygen intermediates; 2) the stimulation is associated with the assembly of the cytosolic components of NADPH oxidase on the plasma membrane, the process that corresponds to the activation of the enzyme; 3) neutrophils and monocytes of chronic granulomatous disease patients do not respond to beta-amyloid peptides with the stimulation of reactive oxygen intermediate production. Data are also presented that the activation of NADPH oxidase requires that beta-amyloid peptides be in fibrillary state, is inhibited by inhibitors of tyrosine kinases or phosphatidylinositol 3-kinase and by dibutyryl cyclic AMP, and is potentiated by interferon-gamma or tumor necrosis factor-alpha.
Amyloid beta-Peptides↗
Inflammatory mechanisms in Alzheimer's disease.
Alzheimer's disease is aetiologically heterogeneous, but the pathogenesis is often considered to be initiated by the deposition of amyloid fibrils, followed by neuritic tau pathology and neuronal death. A variety of inflammatory proteins has been identified in the brains of patients with Alzheimer's disease post mortem. In this article, Piet Eikelenboom and colleagues review evidence to suggest that the inflammatory processes are intimately involved in several crucial events in the pathological cascade. This suggests possibilities for the treatment of Alzheimer's disease with anti-inflammatory drugs.
Alzheimer Disease↗
The importance of inflammatory mechanisms in Alzheimer disease.
Lesions in such chronic neurodegenerative disorders as Alzheimer disease (AD), Parkinson disease, the parkinsonism dementia complex of Guam, and amyotrophic lateral sclerosis have associated with them a variety of proteins known to be involved in inflammatory processes. This is particularly true of AD, where inflammatory reactions are thought to be important contributors to the neuronal loss. Proteins present include complement proteins, complement inhibitors, acute phase reactants, inflammatory cytokines, proteases, and protease inhibitors. Studies of cultured human astrocytes and microglia, obtained from postmortem brain, have established that nearly all of these proteins are produced by one or another of these cell types. Human neurons also produce many inflammatory proteins and their inhibitors, creating complex interactions. Accumulations of amyloid and extracellular tangles apparently act as irritants, causing the activation of complement, the initiation of reactive changes in microglia, and the release of potentially neurotoxic products. Such products include the membrane attack complex, oxygen free radicals, and excess glutamate. Twenty epidemiological studies that have been published to date indicate that populations taking antiinflammatory drugs have a significantly reduced prevalence of AD or a slower mental decline. One small clinical trial with indomethacin showed arrest of the disease over a six-month period. Therapeutic intervention in key inflammatory processes holds great promise for the amelioration of AD and possibly other neurodegenerative disorders.
Alzheimer Disease↗
Inflammatory mechanisms in Alzheimer disease: the role of beta-amyloid/glial interactions.
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Alzheimer Disease↗
Inflammatory mechanisms in diabetes: lessons from the beta-cell.
Inflammation plays an important role in the destruction of pancreatic islet beta-cells that leads to type I diabetes. This involves infiltration of T-cells and macrophages into the islets and local production of inflammatory cytokines such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. Our laboratory has developed several strategies for protecting beta-cells against oxidative stress and cytokine-induced cytotoxicity. These include a cytokine selection strategy that results in cell lines that are resistant to the combined effects of IL-1 beta+IFN-gamma. More recently, we have combined the cytokine selection procedure with overexpression of the antiapoptotic gene bcl-2, resulting in cell lines with greater resistance to oxidative stress and cytokine-induced damage than achieved with either procedure alone. This article summarizes this work and the remarkably divergent mechanisms by which protection is achieved in the different model systems. We also discuss the potential relevance of insights gained from these approaches for enhancing islet cell survival and function in both major forms of diabetes.
Animals↗
The antirheumatic agents sulphasalazine and methotrexate share an anti-inflammatory mechanism.
Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for second-line therapy of rheumatoid arthritis (RA). Although SASP and MTX are commonly used, the mechanism(s) by which these drugs control the inflammation that characterizes RA have remained obscure. Results from my laboratory indicate that these agents share a mode of action; the anti-inflammatory effects of both SASP and MTX are due, in both in vitro and in vivo studies, to their capacity to enhance adenosine release at inflamed sites. This mode of action suggests that the development of agents that directly alter adenosine metabolism may lead to new, more effective and safer antirheumatic drugs than those currently available.
Anti-Inflammatory Agents↗
Anti-inflammatory mechanisms of dietary restriction in slowing aging processes.
Dietary restriction (DR) remains the most powerful and general environmental manipulation of aging processes in laboratory animals with strong beneficial effects on most age-related degenerative changes throughout the body. Underlying the beneficial effects of DR is the attenuation of system-wide inflammatory processes including those occurring within the central nervous system. During normal aging a progressive neuroinflammatory state builds in the brain involving astrocytes and microglia, the primary cellular components of neuroinflammation. DR attenuates the age-related activation of astrocytes and microglia with concomitant beneficial effects on neurodegeneration and cognition. Increasing evidence suggests that common pathways are emerging that link many normal aging inflammatory processes with age-related diseases such as Alzheimer, cancer, diabetes and cardiovascular disease.
Aging↗
Inflammatory mechanisms in neonatal chronic lung disease.
UNLABELLED: Chronic lung disease (CLD) of preterm infants has a multifactorial aetiology. Oxygen toxicity, mechanical injury (barotrauma), volutrauma as well as prenatal and postnatal infections most likely contribute to pulmonary injury in the immature lung of preterm infants. There is sufficient evidence that respiratory distress syndrome and CLD are associated with a significant inflammatory response of the airways and the interstitium of the lungs; besides neutrophils, alveolar and interstitial macrophages immunoreactive for tumour necrosis factor-alpha (TNF-alpha) are found in large numbers. Phagocyte influx is possibly mediated by chemotactic and chemokinetic factors present in the broncho-alveolar secretions: interleukin-8, leukotriene B(4), C5a, elastin fragments, macrophage-inflammatory protein-1alpha and other chemokines. Increased concentrations of soluble selectins and intercellular adhesion molecule-1 in broncho-alveolar secretions and the serum of infants with CLD possibly reflect neutrophil diapedesis. Lipid mediators including leukotrienes, prostacyclin, platelet activating and other mediators such as the pro-inflammatory cytokines TNF-alpha, interleukin-1 and -6, exert various effects on the airways and the vascular system by increasing the microvascular permeability which is one of the most important pathophysiological factors of early CLD. Pulmonary cells of preterm infants may be unable to downregulate inflammation through the expression of the anti-inflammatory cytokine interleukin-10. Inflammatory cells can cause severe lung damage by release of potent proteases (elastase), cytokines and by generation of toxic oxygen radicals (O(2)-, (*)OH). The presence of free elastase activity and the protease-antiprotease imbalance has been well documented. In fact, increased concentrations of products of elastolytic fibre degradation and of oxygen radical mediated lipid peroxidation were detected in infants with CLD. CONCLUSION: The complex interaction between mediators of inflammation and fibrosis has still to be defined. Moreover, the possible interference of inflammation with postnatal lung development especially with the alveolarization process has not been evaluated yet.
Chronic Disease↗
Anti-inflammatory mechanisms of the Tibetan herbal preparation Padma 28 in the vessel wall.
BACKGROUND: The Tibetan herbal preparation Padma 28 has been shown to act as an anti-atherosclerotic agent in advanced peripheral arterial occlusive disease. We tested the effect of aqueous Padma 28 extracts on both the Creactive protein (CRP) induced expression of the pro-inflammatory cell adhesion molecule E-selectin and the anti-atherosclerotic protective enzyme heme oxygenase- 1 (HO-1) in human aortic endothelial cells. METHODS AND RESULTS: According to FACS analysis, quantitative RT-PCR and Western blot, CRP-induced E-selectin expression was completely prevented by aqueous Padma 28 extracts. Additionally, Padma 28 mediated an up to 60-fold upregulation of HO-1 mRNA as measured by quantitative RT-PCR. This upregulation could also be demonstrated on the protein level. CONCLUSION: Aqueous extracts of the Tibetan herbal preparation Padma 28 inhibit CRP-induced expression of the inflammatory cell adhesion molecule E-selectin and lead to upregulation of the vascular protective enzyme HO-1 in human aortic endothelial cells. These properties may be responsible for its anti-atherosclerotic effects in peripheral arterial occlusive disease.
Anti-Inflammatory Agents↗
Inflammatory mechanisms and nocturnal asthma.
The results of recent research strongly suggest that airway inflammation, which may increase at night as a result of circadian troughs in blood epinephrine and cortisol concentrations, underlies the bronchial hyperresponsiveness that is almost certainly a major contributor to the pathogenesis of nocturnal asthma. This article reviews what is known about the nature and complex interactions of the inflammatory cells and mediators that may be involved in asthma, with particular emphasis on nocturnal asthma. The roles of platelet-activating factor antagonists, corticosteroids, and theophylline in suppressing this response also are discussed.
Adenosine↗