Correlation between different gene expression assays designed to measure trans-activation potencies of systemic glucocorticoids

Jaffuel, Dany; Roumestan, Caroline; Balaguer, Patrick; Henriquet, Corinne; Gougat, Claire; Bousquet, J; Demoly, Pascal; Mathieu, Marc

doi:10.1016/s0039-128x(00)00235-x

Cited by 27 publications

(16 citation statements)

References 34 publications

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“…Although these clinical data suggest a therapeutic advantage for BTM over DXM (4), in the present in vitro study, BTM and DXM achieved similar effects. This is consistent with previous reports that found no significant differences between BTM and DXM when the nuclear receptor-dependent genomic effect was measured as indicator of relative potency (14). Likewise, DXM and BTM showed similar dose-response patterns of SP-B expression in H441 cells and in human type II pneumocytes (28).…”

Section: Discussionsupporting

confidence: 92%

Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway

Ladenburger

Schumacher

Kramer

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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The respiratory distress syndrome (RDS) contributes to perinatal morbidity and mortality associated with preterm birth. Surfactant protein B (SP-B) is decreased in RDS. Both maternal antenatal steroid administration and chorioamnionitis reduce the incidence and severity of RDS. An important mediator in chorioamnionitis is IL-6 using the JAK-STAT signaling pathway for signal transduction. We hypothesized that the steroids, betamethasone (BTM) and dexamethasone (DXM), and IL-6 had synergistic effects on SP-B gene expression and STAT3 phosphorylation in H441 cells. DXM and BTM increased SP-B mRNA levels by 16.5 (13.3)-fold and IL-6 alone by 2.3-fold. After 48-h exposure of cells to DXM or BTM, IL-6 caused a significantly greater increase in SP-B mRNA levels (28.1-fold) than IL-6 or glucocorticoids alone. Whereas IL-6 stimulated tyrosine phosphorylation of STAT3 in a time- and dose-dependent way, DXM and BTM had no effect on STAT3 phosphorylation. Both DXM and BTM could potentiate IL-6-induced phosphorylation of STAT3. The synergism of glucocorticoids and IL-6 on SP-B gene expression and the effect of glucocorticoids on IL-6-induced STAT3 phosphorylation could be blocked by a JAK inhibitor. Expression level analysis showed that glucocorticoids increased the expression of the IL-6-binding α-subunit receptor (IL-6R) on mRNA and protein level. Our findings could represent an example of a pulmonary regulation system in which one role of glucocorticoids is to increase the effect of a cytokine by upregulation of its receptor. The described in vitro interaction of IL-6 and glucocorticoids could help explain the clinical observation that prenatal inflammation in preterm babies with antenatal steroid administration can attenuate severity of RDS.

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Section: Discussionsupporting

confidence: 92%

Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway

Ladenburger

Schumacher

Kramer

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Different glucocorticoids can have different transcriptional potencies in different tissues, which results in tissue differences in magnitude of effect that can bypass the classical order of glucocorticoid potencies (Jaffuel et al . 2000, 2001). For example, in the classical order, TMC would be regarded as 5 times less potent than DEX, but it is equipotent with DEX in its diabetogenic effect because it induces similar increases in the activity of the gluconeogenic enzyme tyrosine aminotransferase (Jaffuel et al .…”

Section: What Is the Risk Of Laminitis Following Glucocorticoid Adminmentioning

confidence: 99%

Glucocorticoid therapy and the risk of equine laminitis

Cornelisse

Robinson

2011

Equine Veterinary Education

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Summary Although glucocorticoids have been used successfully for the treatment of noninfectious inflammatory diseases of horses for more than 35 years, their use has been attended by a fear of the induction of laminitis. This paper reviews the evidence for this fear and the possible mechanisms whereby glucocorticoids could participate in laminitis induction. Although the association of laminitis with elevated serum cortisol in pituitary pars intermedia dysfunction suggests that chronic exposure to glucocorticoids may be part of laminitis pathogenesis, review of published reports and databases suggests that glucocorticoid‐induced laminitis is a relatively rare occurrence. However, several of the actions of glucocorticoids are similar to those known to be involved in laminitis pathogenesis. Glucocorticoid administration can induce insulin resistance, lead to vascular dysfunction that potentiates vasoconstriction, and interfere with keratinocyte proliferation and differentiation as well as matrix integrity, all mechanisms that could possibly induce laminitis. Drug formulation, dose and route of administration, and the systemic and hoof disease history of the horse must all be considered when assessing laminitis risk during glucocorticoid treatment. Generally, local glucocorticoid administration presents little risk as does systemic treatment of recurrent airway obstruction without concurrent disease. Caution should be used however in horses that are overweight and/or insulin resistant, or have had a recent bout of acute laminitis of alimentary or endotoxic origin. Overall, however, the risk of laminitis after glucocorticoid treatment, especially local use, is acceptable compared to the many benefits of these drugs.

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“…TA concentrations in aqueous, iris-ciliary body and vitreous were similar and much lower. On post-injection day 30, the concentration in both neuroretina and RPE/choroid was >150 ng/g, which is much higher than the 1.7–4.3 ng/ml of TA 50% effective concentration to trans-repress many genes encoding pro-inflammatory mediators or cytokines in many cell lines 23 24. The half-life of TA was 6.81 days in the neuroretina and 10.4 days in the RPE/choroid.…”

Section: Discussionmentioning

confidence: 89%

Characterisation of systemic and ocular drug level of triamcinolone acetonide following a single sub-Tenon injection

Nan

Sun

et al. 2010

British Journal of Ophthalmology

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AIM To characterise the pharmacokinetics of triamcinolone acetonide (TA) in various ocular tissues following a single sub-Tenon injection. METHODS Twenty-one Chinchilla adult pigmented rabbits received sub-Tenon injection of TA (40 mg in 0.4 ml) in their right eyes. Three animals were killed at each designated time points (3 h, 1 day, 3 days, 7 days, 14 days, 21 days and 30 days) and the globes were snap frozen and dissected into aqueous, iris-ciliary body, vitreous, neuroretina and retinal pigment epithelium (RPE)/choroid. The concentrations of TA in the various ocular tissues were analysed using ultra-performance liquid chromatography, coupled with tandem mass spectrometric detection. RESULTS TA concentration followed a mono-exponential decrease over the study period in all ocular tissues of the injected eyes. The concentration was much higher in the RPE/choroid (892.14+/-558.11 ng/g at post-injection day 30) than in the other tissues (171.65+/-136.40 ng/g in neuroretina, 15.65+/-23.06 ng/ml in vitreous, 3.76+/-1.79 ng/g in iris-ciliary body, 2.64+/-0.96 ng/ml in aqueous at post-injection day 30). The TA level in the RPE/choroid had the lowest coefficient of logarithmic regression (0.07 in RPE/choroid, 0.10 in neuroretina, 0.11 in vitreous, 0.17 in iris-ciliary body, 0.18 in aqueous), indicating a 2.6 times slower clearance than in aqueous. The half-life of TA was 10.4 days in RPE/choroid. TA was detectable in the fellow eyes and was also detectable at very low levels in all blood samples during the entire study period. CONCLUSION TA was mostly cleared from RPE/choroid and retina in a mono-exponential mode. TA was above the therapeutic level for at least 30 days following a sub-Tenon injection.

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Correlation between different gene expression assays designed to measure trans-activation potencies of systemic glucocorticoids

Cited by 27 publications

References 34 publications

Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway

Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway

Glucocorticoid therapy and the risk of equine laminitis

Characterisation of systemic and ocular drug level of triamcinolone acetonide following a single sub-Tenon injection

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