Effects of topical corticosteroids on inflammatory mediator–induced eicosanoid release by human airway epithelial cells

Aksoy, Mark O.; Li, Xiu Xia; Borenstein, Michael; Yi, Yang; Kelsen, Steven G.

doi:10.1016/s0091-6749(99)70183-1

Cited by 46 publications

(30 citation statements)

References 37 publications

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“…27), had no effect on the expression of luciferase measured at 5 h or on the ability of dexamethasone to promote GRE-dependent transcription (data not shown). These data are thus consistent with the inability of BEAS-2B cells to synthesize PGI 2 (32). However, in dexamethasone (1 M)-treated cells RO3244794 produced a graded, parallel rightwards displacement (12-and 36-fold at 10 and 30 nM, respectively) of the taprostene E/[A] curve (Fig.…”

Section: Affinity Of Ro3244794 For Antagonizing Taprostene-induced Resupporting

confidence: 84%

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Wilson

Shen²,

Rider³

et al. 2009

The Journal of Immunology

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Prostacyclin receptor (IP-receptor) agonists display anti-inflammatory and antiviral activity in cell-based assays and in preclinical models of asthma and chronic obstructive pulmonary disease. In this study, we have extended these observations by demonstrating that IP-receptor activation also can enhance the ability of glucocorticoids to induce genes with anti-inflammatory activity. BEAS-2B bronchial epithelial cells stably transfected with a glucocorticoid response element (GRE) luciferase reporter were activated in a concentration-dependent manner by the glucocorticoid dexamethasone. An IP-receptor agonist, taprostene, increased cAMP in these cells and augmented luciferase expression at all concentrations of dexamethasone examined. Analysis of the concentration-response relationship that described this effect showed that taprostene increased the magnitude of transcription without affecting the potency of dexamethasone and was, thus, steroid-sparing in this simple system. RO3244794, an IP-receptor antagonist, and oligonucleotides that selectively silenced the IP-receptor gene, PTGIR, abolished these effects of taprostene. Infection of BEAS-2B GRE reporter cells with an adenovirus vector encoding a highly selective inhibitor of cAMP-dependent protein kinase (PKA) also prevented taprostene from enhancing GRE-dependent transcription. In BEAS-2B cells and primary cultures of human airway epithelial cells, taprostene and dexamethasone interacted either additively or cooperatively in the expression of three glucocorticoid-inducible genes (GILZ, MKP-1, and p57kip2) that have anti-inflammatory potential. Collectively, these data show that IP-receptor agonists can augment the ability of glucocorticoids to induce anti-inflammatory genes in human airway epithelial cells by activating a cAMP/PKA-dependent mechanism. This observation may have clinical relevance in the treatment of airway inflammatory diseases that are either refractory or respond suboptimally to glucocorticoids.

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Section: Affinity Of Ro3244794 For Antagonizing Taprostene-induced Resupporting

confidence: 84%

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Wilson

Shen²,

Rider³

et al. 2009

The Journal of Immunology

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“…Together, these findings support the postulate that concomitant activation of extracellular signal-regulated kinase (in the current study via PAR 2 ; Kawao et al, 2005) and induction of COX-2 by lipopolysaccharide stimulates maximum PGE 2 synthesis in human airway epithelial cells (Petrovic et al, 2006). These synergistic effects of SLIGRL-NH 2 and lipopolysaccharide on PGE 2 production were not observed in cells cotreated with dexamethasone, probably due to the well documented inhibitory actions of glucocorticoids on cytokine-induced expression of important components of the PGE 2 synthetic pathway, including COX-2 (Mitchell et al, 1994;Aksoy et al, 1999;Chivers et al, 2006). PAR 2 -activating peptides such as SLIGRL-NH 2 also stimulate the release of PGE 2 in intact airway preparations such as the mouse trachea (Lan et al, 2001;Henry et al, 2005).…”

Section: Influence Of Dexamethasone On Par 2 Function In Airways 627mentioning

confidence: 46%

Influence of Dexamethasone on Protease-Activated Receptor 2-Mediated Responses in the Airways

Saleh

Mann²,

Peters³

et al. 2007

J Pharmacol Exp Ther

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“…Moreover, the cellular content is another source of information and also a source of the mediators. The similarity between BALF and EBC allows us to draw a conclusion that the mediators we measured in both materials come from the same source which might be phagocytes present in airway lumen, epithelial cells and pneumocytes [15]. The higher concentrations of lipid mediators in BALF compared to EBC might be derived from cells present in the fluid and to an unknown extent from mediators that are washed out from the epithelial lining fluid.…”

Section: Discussionmentioning

confidence: 72%

Correlation between Eicosanoids in Bronchoalveolar Lavage Fluid and in Exhaled Breath Condensate

et al. 2011

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Abstract. Exhaled breath condensate (EBC) has been increasingly used as a new and non-invasive method to study airway inflammation. In this study we have compared the concentrations of lipid mediators in EBC with concentrations in bronchoalveolar lavage fluid (BALF). We included 37 patients undergoing bronchoscopy (12 sarcoidosis, 12 COPD, 6 lung cancer, 5 chronic cough, 1 Wegener's granulomatosis, 1 sclerodermia). Patients were not allowed to have exacerbation or any change in concomitant medication for at least 4 weeks prior to the study. In all patients, EBC was collected immediately prior to the bronchoscopy. The levels of cys-LTs, LTB4, 8-isoprostane were significantly higher in BALF compared to EBC (p < 0.0001, p < 0.001, p < 0.0001 for cys-LTs, LTB4, 8-isoprostane respectively). Moreover, there was a strong positive correlation between both leukotriene B4 and 8-isoprostane in BALF and EBC (r = 0.53 and r = 0.79, p < 0.01, respectively) in patients with sarcoidosis and COPD but there was no correlation between eicosanoids BALF and EBC in patients with chronic cough and lung cancer. This is the first study to compare EBC and BALF in different lung diseases which demonstrated significant correlations between the levels of eicosanoids in BALF and EBC in patients with COPD and sarcoidosis. EBC may be useful in measuring inflammation in several inflammatory lung diseases.

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Effects of topical corticosteroids on inflammatory mediator–induced eicosanoid release by human airway epithelial cells

Cited by 46 publications

References 37 publications

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Influence of Dexamethasone on Protease-Activated Receptor 2-Mediated Responses in the Airways

Correlation between Eicosanoids in Bronchoalveolar Lavage Fluid and in Exhaled Breath Condensate

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