Dexamethasone and thyroid hormone pretreatment upregulate alveolar epithelial fluid clearance in adult rats

Folkesson, Hans G.; Norlin, Andreas; Wang, Yibing; Abedinpour, Parisa; Matthay, Michael A.

doi:10.1152/jappl.2000.88.2.416

Cited by 74 publications

(66 citation statements)

References 50 publications

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“…with 5 mg/kg body weight of Dex (Sigma-Aldrich) dissolved in a 0.9% NaCl solution. Control ADX rats were treated with 0.9% NaCl alone (38). At the same time of Dex supplement, hypoxia exposure was done in the ADX rats of the combined administration group.…”

Section: Adrenalectomy and Dex Supplementmentioning

confidence: 99%

Upregulations of Glucocorticoid-Induced Leucine Zipper by Hypoxia and Glucocorticoid Inhibit Proinflammatory Cytokines under Hypoxic Conditions in Macrophages

Wang

Song

et al. 2012

The Journal of Immunology

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Hypoxia and inflammation often develop concurrently in numerous diseases, and the influence of hypoxia on natural evolution of inflammatory responses is widely accepted. Glucocorticoid-induced leucine zipper (GILZ) is thought to be an important mediator of anti-inflammatory and immune-suppressive actions of glucocorticoid (GC). However, whether GILZ is involved in hypoxic response is still unclear. In this study, we investigated the effects of hypoxic exposure and/or the administration of dexamethasone (Dex), a synthetic GC on GILZ expression both in vitro and in vivo, and further explored the relationship between GILZ and proinflammatory cytokines IL-1β, IL-6, and TNF-α under normoxic and hypoxic conditions. We found that hypoxia not only remarkably upregulated the expression of GILZ, but also significantly enhanced Dex-induced expression of GILZ in macrophages and the spleen of rats. ERK activity is found involved in the upregulation of GILZ induced by hypoxia. Inhibiting the expression of GILZ in RAW264.7 cells using specific GILZ small interfering RNA led to a significant increase in mRNA production and protein secretion of IL-1β and IL-6 in hypoxia and abrogated the inhibitory effect of Dex on expression of IL-1β and IL-6 in hypoxia. We also found that adrenal hormones played pivotal roles in upregulation of GILZ expression in vivo. Altogether, data presented in this study suggest that GILZ has an important role not only in adjusting adaptive responses to hypoxia by negatively regulating the activation of macrophages and the expression of proinflammatory cytokines, but also in mediating the anti-inflammatory action of GC under hypoxic conditions.

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Section: Adrenalectomy and Dex Supplementmentioning

confidence: 99%

Upregulations of Glucocorticoid-Induced Leucine Zipper by Hypoxia and Glucocorticoid Inhibit Proinflammatory Cytokines under Hypoxic Conditions in Macrophages

Wang

Song

et al. 2012

The Journal of Immunology

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“…Steroids are used in some pulmonary oedema patients and they significantly upregulate alveolar fluid clearance in animals [12,14]. Although the exact therapeutic role of steroids in pulmonary oedema is not yet clear, it is well documented that steroids significantly activate expression of a-ENaC [13,31,32].…”

Section: Cigarette Smoke Inhibitsmentioning

confidence: 99%

“…Steroids have been used in treating some ALI patients and are known to activate ENaC a-subunit expression and to upregulate alveolar epithelial fluid clearance [12][13][14]. Therefore, possible interplay between CSC and dexamethasone was examined.…”

mentioning

confidence: 99%

Cigarette smoke condensate inhibits ENaC -subunit expression in lung epithelial cells

Ferro²,

Chu³

2007

European Respiratory Journal

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Cigarette smoke has been associated with lung fluid accumulation and increased risk of acute respiratory distress syndrome. It was postulated that ENaC a-subunit, which plays a critical role in lung fluid absorption, is affected by cigarette smoke.Cigarette smoke condensate (CSC) was used to treat a human lung epithelial cell line. ENaC a-subunit expression was measured using immunoblotting, quantitative PCR and promoterreporter assays.The current authors found that CSC, without affecting cell survival, suppressed a-subunit expression at the transcriptional level in a dose-and time-dependent fashion. This suppression is neither related to nicotine nor due to an increase of hydrogen peroxide levels in CSC-treated cells. CSC also suppressed a-subunit core promoter activity. Dexamethasone, which activates the core promoter, was able to attenuate the inhibitory effect of CSC. However, in the presence of CSC, dexamethasone was unable to elicit a full-scale activation of a-subunit expression. This inhibition of dexamethasone was partially reversed by withdrawal of CSC.The present results demonstrate that cigarette smoke condensate inhibits ENaC a-subunit expression at the transcriptional level through its promoter. This inhibition could be reversed by dexamethasone. The results also suggest that higher doses of dexamethasone may be needed to activate a-subunit expression in smokers' lungs compared with nonsmokers' lungs, and that quitting smoking might improve the effectiveness of dexamethasone.

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“…Fluid absorption occurs in near-term lungs (6,17,35,37,45) and is induced/ stimulated by cortisol and triiodothyronine (2,20,48) and labor-released epinephrine (17,35,45).…”

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confidence: 99%

Oxytocin-induced labor augments IL-1β-stimulated lung fluid absorption in fetal guinea pig lungs

Nair¹,

Li²,

Bhattacharjee³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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-We tested the hypothesis that oxytocin-induced labor augmented IL-1␤-induced/ -stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1␤ was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3, oxytocin was administered, and fetuses were delivered by abdominal hysterotomy at 61 and by oxytocin-induced birth at 68 days gestation. Delivered fetuses were instilled with isosmolar 5% albumin into the lungs, and lung fluid movement was measured over 1 h by mass balance. Lung fluid absorption was induced in 61-day and stimulated in 68-day gestation lungs by IL-1␤. Labor induction by oxytocin augmented IL-1␤-induced/-stimulated lung fluid absorption. Metyrapone pretreatment did not affect oxytocin-induced/-stimulated lung fluid absorption, while completely blocking IL-1␤-induced/-stimulated fluid absorption. Fetal lung fluid absorption, when present, was always propranolol and amiloride sensitive, suggesting that ␤-adrenoceptor stimulation and amiloridesensitive sodium channels were critical for fluid absorption. Epithelial sodium channel and Na-K-ATPase subunit expressions were both increased by IL-1␤, but not further by oxytocin. Our results indicate that IL-1␤ release into the maternal blood circulation positively affects lung maturation due to the IL-1␤-induced release of cortisol and thus prepares the lungs for the epinephrine surge associated with labor.␤-adrenoceptors; cortisol; epinephrine; prenatal lung development; sodium transport CYTOKINES, SUCH AS INTERLEUKIN-1 (IL-1), can be important during pregnancy, because IL-1 has been detected in the placenta and amniotic fluid (12,44). In this regard, interleukins have been proposed as a signal for parturition onset, as cytokines can stimulate prostaglandin biosynthesis (41). During normal pregnancies, IL-1 is present in the amniotic fluid in low concentrations, but during preterm labor much higher amniotic fluid IL-1 concentrations are present (44). Intrauterine infection/inflammation may further elevate cytokine levels, the highest activity being attributable to IL-1␤ (44). Many prematurely born infants suffer from fetal infection and/or respiratory distress syndrome (RDS), both of which are important reasons for mortality of premature babies. Recent human data suggest that ion transport abnormalities across lung epithelial cells, i.e., an incomplete transition of lung fluid secretion to lung fluid absorption, can contribute to RDS development (1). Factors accelerating ion transport across alveolar cells may thus have benefits for the resolution of RDS. Recent experimental data have suggested that proinflammatory cytokines could also promote lung maturation (9,14,26,47). IL-1␣ increased mRNA surfactant protein expression and improved lung compliance in fetal rabbits (9). IL-1␣ also improved postnatal lung function with increased surfactant pool size without eliciting systemic inflammatory responses in lambs (14, 47). We recently reported that IL-...

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Dexamethasone and thyroid hormone pretreatment upregulate alveolar epithelial fluid clearance in adult rats

Cited by 74 publications

References 50 publications

Upregulations of Glucocorticoid-Induced Leucine Zipper by Hypoxia and Glucocorticoid Inhibit Proinflammatory Cytokines under Hypoxic Conditions in Macrophages

Upregulations of Glucocorticoid-Induced Leucine Zipper by Hypoxia and Glucocorticoid Inhibit Proinflammatory Cytokines under Hypoxic Conditions in Macrophages

Cigarette smoke condensate inhibits ENaC -subunit expression in lung epithelial cells

Oxytocin-induced labor augments IL-1β-stimulated lung fluid absorption in fetal guinea pig lungs

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