Endothelin‐1 stimulates human monocytes <i>in vitro</i> to release TNF‐α , IL‐1β and IL‐6

Helset, E.; Sildnes, T.; Seljelid, Rolf; Konopski, Zbigniew

doi:10.1155/s0962935193000596

Cited by 61 publications

(44 citation statements)

References 6 publications

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“…IL-1β has been implicated in the migration of inflammatory cells in BALF of symptomatic asthmatic patients (Broide et al, 1992). In vitro studies have shown that IL-1β increases ET-1 release from cultured airway epithelial cells (Nakano et al, 1994), and, conversely, IL-1β is found to be produced by ET-1 stimulation of human macrophages (Helset et al, 1993). Over the last years, TNF-α has gained attention as an important mediator in inflammatory disorders, such as asthma (Kips et al, 1993), and it should be noted that the synthesis of TNF-α is preceded by the syntesis of ET-1 (Finsnes et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Gamze

Mehmet²,

Deveci³

et al. 2007

Exp Mol Med

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Endothelin (ET) receptor antagonists have been developed to produce a reduction of ET related effects in various diseases, as well as in animal models of airway inflammation. We aimed to investigate the anti-inflammatory potential of bosentan on a rat model of emphysema. Thirty Wistar male rats were classified as control group (group 1), intratracheally (i.t.) instilled with saline, treated with vehicle solution; elastase group (group 2), i.t. instilled with porcine pancreatic elastase (PPE), treated with vehicle solution; and PPE+bosentan group (group 3), i.t. instilled with PPE, treated with bosentan. The levels of TNF-α, IL-1β, IL-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and lung tissue, cell counts in BALF, and histologic analysis of all groups were evaluated. Neutrophile granulocytes (NG) and alveolar macrophages (AM) were increased more in group 2 than in group 1 (P ＜ 0.001, P = 0.04, respectively). Compared with group 2, neutrophil granulocyte (NG) and alveolar macrophages (AM) counts were decreased in group 3 (P ＜ 0.001). Histological examination confirmed a diffuse neutrophilic inflammation and irregular alveolar air space enlargement in group 2. Treatment with bosentan partially reduced the enlarged lung volumes. Compared with group 1, the BALF levels of TNF-α and IL-6, and the lung tissue levels of IL-1β, IL-6, and IL-8 were increased in group 2 (P = 0.028, P = 0.005, P = 0.001, P = 0.019, P ＜ 0.001, respectively). The TNF-α and IL-8 levels of BALF (P = 0.007, P = 0.001, respectively), and the TNF-α, IL-1β, IL-6, and the IL-8 levels of lung tissue (P = 0.031, P = 0.017, P = 0.007, P ＜ 0.001) were decreased in group 3 compared to group 2. In conclusion, bosentan decreased the inflammatory response by reducing numbers of inflammatory cells and proinflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Gamze

Mehmet²,

Deveci³

et al. 2007

Exp Mol Med

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“…It is well established that infusion of LPS stimulates release of inflammatory mediators such as TNF-α, IL-8, and ET-1 (3,21,39). Similarly, ET-1 stimulates monocytes and macrophages to release TNF-α and IL-8 (11,12), and enhanced plasma concentrations of TNF-α, IL-8, and ET-1 were found after 4 h in endotoxemic subjects (19). Finally, increases in ET-1 and TNF-α were found to be consistent in a study that used endothelin receptor antagonist bosentan (41).…”

Section: Animals and Treatmentsmentioning

confidence: 99%

Time-dependent expression of endothelin-1 in lungs and the effects of TNF-α blocking peptide on acute lung injury in an endotoxemic rat model

et al. 2011

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Endothelin (ET)-1 is a potent vasoconstrictor that has been implicated in the pathogenesis of a number of diseases, and some studies suggest that circulating ET-1 is elevated in sepsis. The present study investigated whether ET plays a role in sepsis-mediated acute lung injury and whether its expression could be down regulated by blockade of TNF-α in septic lung. Male Wistar rats at 8 weeks of age were administered with either saline or lipopolysaccharide (LPS) at different time points (1, 3, 6 and 10 h) and various tests were then performed. The features of acute lung injury were observed at 1 h after LPS administration, which gradually became severe with time. Systolic and diastolic pressures were reduced just about one hour after LPS administration, whereas pulmonary TNF-α levels were significantly increased at various time points after LPS administration. LPS induced a time-dependent expression of ET-1 and ET A receptor in the lungs compared to control, peaking and increasing by 3 fold at 6 h after induction of endotoxemia, whereas levels of ET B receptor, which has vasodilating effects, were remarkably down regulated time-dependently. We conclude that time-dependent increase of ET-1 and ET A receptor with the down regulation of ET B receptor may play a role in the pathogenesis of acute lung injury in endotoxemia. Finally, treatment of LPS-administered rats with TNF-α blocking peptide for three hours significantly suppressed levels of pulmonary ET-1. These data taken together, led us to conclude that differential alteration in ET expression and its receptors may be mediated by TNF-α and may, in part, account for the pathogenesis of acute lung injury in endotoxemia.The presence of multiple organ dysfunction syndrome (MODS) is the most important determinant of prognosis in endotoxemia and sepsis (6), and the lung is the most common organ with the most infection, involved in a fatal sepsis that leads to rapid onset of a life-threatening respiratory insufficiency (6). The development of acute lung injury (ALI) as well acute respiratory distress syndrome (ARDS) is common in those cases. Animal models for human ALI and ARDS are generated by systemic infusion of live bacteria or endotoxin of gram-negative bacteria (9). Cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) have been identified as important pathogenic mediators of endotoxin-induced ALI (38). During sepsis, the alveolar compartmentalization is lost, allowing passage of cytokines, which eventually can be released into the bloodstream by other organs, and ultimately to the pulmonary endothelium. These cytokines, especially IL-1, TNF-α and IL-8, have important roles in lung

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“…Interestingly, there seems to be a link between ET-1 and TNF-a, since in vitro studies have shown that TNF-a may induce ET-1 production in airway epithelial cells [18±21]. Conversely, ET-1 may also stimulate the biosynthesis of TNF-a [22,23]. In addition, to study the generation of ET-1 in both a neutrophilic and eosinophilic airway inflammation, the synthesis and release of TNF-a in relation to ET-1 in these in vivo models was examined.…”

mentioning

confidence: 99%

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

et al. 2000

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Endothelin‐1 (ET‐1) is a strong bronchoconstrictor which possesses pro‐inflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET‐1 synthesis, in an inflammation dominated by neutrophilic granulocytes, is as pronounced as previously demonstrated in an airway inflammation dominated by eosinophils. Moreover, the authors compared the production of ET‐1 and tumour necrosis factor (TNF)‐α in rat lungs following intratracheal instillation of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sephadex (SDX) (eosinophilic). The lung tissue ET‐1 messenger ribonucleic acid (mRNA) expression was not increased in LPS treated animals whereas a six‐fold increase was measured after 30 min in the SDX group (p<0.05). TNF‐α mRNA signals increased early following LPS instillation, peaking at 2 h, whereas elevated TNF‐α mRNA in the SDX model was observed at 24 h. The ET‐1 concentrations in bronchoalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after both LPS and SDX exposure. At 24 h no further rise in ET‐1 levels was observed in the LPS model, while a substantial increase in the ET‐1 concentration was measured in the SDX group (p<0.05). The TNF‐α concentrations in BALF rose considerably at 3 h in the LPS group, but was nearly abolished at 24 h. In SDX challenged animals however, an increase in BALF‐TNF‐α did not occur until 24 h postchallenge. In conclusion, intratracheal instillation of lipopolysaccharide, leading to a purely neutrophilic lung inflammation, does not induce synthesis of endothelin‐1. This is in contrast to observations during an eosinophilic airway inflammation, indicating a specific role of endothelin‐1 in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin‐1 synthesis was observed by high levels of tumour necrosis factor‐αin vivo.

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Endothelin‐1 stimulates human monocytes in vitro to release TNF‐α , IL‐1β and IL‐6

Cited by 61 publications

References 6 publications

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Time-dependent expression of endothelin-1 in lungs and the effects of TNF-α blocking peptide on acute lung injury in an endotoxemic rat model

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

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