Glucocorticoids Inhibit Proliferation and Interleukin-4 and Interleukin-5 Secretion by Aeroallergen-Specific T-Helper Type 2 Cell Lines

Crocker, I.C.; Church, Martin K.; Newton, Sean C.; Townley, Robert G.

doi:10.1016/s1081-1206(10)63075-x

Cited by 32 publications

(14 citation statements)

References 32 publications

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“…2a,b). The IC 50 of hydrocortisone on NHE1‐depedent pH i recovery was 250 nM, which is a similar concentration to that reported as needed in human T‐helper (Th)2 cells for cytokine secretion and proliferation (Crocker et al, 1998). In this study, the IC 50 of dexamethasone for NHE1‐depedent pH i recovery was found to be 1 nM, which is 10‐fold lower than that assessed by genomic studies (Liberman et al, 2009).…”

Section: Discussionsupporting

confidence: 76%

Non‐genomic rapid inhibition of Na⁺/H⁺‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

Chang¹,

Wang

Huang³

et al. 2010

Journal Cellular Physiology

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Glucocorticoids (GCs) have been employed as immunosuppressive agents for many years. However, it is still unclear how GCs instantly uncouple T cells from acute stressful inflammatory. In terms of time scale, the genomic activity of the classic GC receptor cannot fulfill this role under crisis; but a rapid non-genomic response can. In a previous study, intracellular acidification was found to be due to a rapid non-genomic inhibition of Na(+)/H(+)-exchange 1 (NHE1) and this event led to the immunosuppression of T cell proliferation by progesterone. The aim of this study was to examine whether there is a rapid acidification response caused by an inhibition of NHE1 activity and to explore the differential non-genomic effect on immunosuppression of hydrocortisone and dexamethasone. The IC(50) values for NHE1-dependent pH(i) recovery by hydrocortisone and dexamethasone are 250 and 1 nM, respectively. Co-stimulation of GCs with phytohemagglutinin (PHA) is able to inhibit PHA-induced IL-2 secretion, IL-4 secretion, and T-cell proliferation. Furthermore, apoptosis in PHA-activated T cells is not induced by hydrocortisone but by dexamethasone. The mechanism of immunosuppression on proliferation by dexamethasone was found to be different of hydrocortisone and seems to involve cytotoxicity against T cells. Moreover, apoptosis induced by dexamethasone and impermeable dexamethasone-bovine serum albumin suggests that the apoptotic immunosuppression occurs through both the plasma membrane and cytoplasmic sites. The rapid inhibitory responses triggered by GCs would seem to release T cells instantly when an acute stress-related response is needed. Nonetheless, the apoptotic immunosuppression by dexamethasone is attributable to its severe cytotoxicity.

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Section: Discussionsupporting

confidence: 76%

Non‐genomic rapid inhibition of Na⁺/H⁺‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

Chang¹,

Wang

Huang³

et al. 2010

Journal Cellular Physiology

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“…Based on the outcomes measured in this study, the results obtained with BUD Turbuhaler1 (400 mg b.i.d) were most comparable to MF DPI 100 mg b.i.d. These findings suggest that MF DPI is more potent than BUD Turbuhaler1, which is in agreement with in vitro findings [4,5,7]. However, only one dose of BUD was used in this study, and it is possible that higher doses of BUD would show an efficacy comparable to that of MF.…”

Section: Evaluation Of Safetysupporting

confidence: 89%

Comparison of the efficacy and safety of mometasone furoate dry powder inhaler to budesonide Turbuhaler

Bousquet¹,

D’Urzo²,

Hébert³

et al. 2000

Eur Respir J

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Significant superiority (p<0.05) was also seen in scores for several secondary efficacy variables when MF DPI was compared with BUD Turbuhaler1 treatment. MF DPI 200 mg b.i.d was comparable to MF DPI 400 mg b.i.d in therapeutic benefit. The incidence of oral candidiasis was no more than 3% in any group. All treatments were well tolerated.A total daily dose of 400 mg of mometasone furoate administered by dry powder inhaler provides a well-tolerated treatment for patients with moderate persistent asthma and results in a significantly greater improvement, when compared to a daily dose of 800 mg BUD Turbuhaler1 in the parameters measured in this study. Eur Respir J 2000; 16: 808±816.

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“…GCs have already been reported to reduce proliferation in various cell types [31], [32], [33], [34]. Despite extensive research effort, there is no consensus on the mechanisms by which GCs may reduce cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Rat Fetal Beta-Cell Development by Maternal Exposure to Dexamethasone during Different Time-Windows

et al. 2011

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AimGlucocorticoids (GCs) take part in the direct control of cell lineage during the late phase of pancreas development when endocrine and exocrine cell differentiation occurs. However, other tissues such as the vasculature exert a critical role before that phase. This study aims to investigate the consequences of overexposure to exogenous glucocorticoids during different time-windows of gestation for the development of the fetal endocrine pancreas.MethodsPregnant Wistar rats received dexamethasone acetate in their drinking water (1 µg/ml) during the last week or throughout gestation. Fetuses and their pancreases were analyzed at day 15 and 21 of gestation. Morphometrical analysis was performed on pancreatic sections after immunohistochemistry techniques and insulin secretion was evaluated on fetal islets collected in vitro.ResultsDexamethasone given the last week or throughout gestation reduced the beta-cell mass in 21-day-old fetuses by respectively 18% or 62%. This was accompanied by a defect in insulin secretion. The alpha-cell mass was reduced similarly. Neither islet vascularization nor beta-cell proliferation was affected when dexamethasone was administered during the last week, which was however the case when given throughout gestation. When given from the beginning of gestation, dexamethasone reduced the number of cells expressing the early marker of endocrine lineage neurogenin-3 when analyzed at 15 days of fetal age.ConclusionsGCs reduce the beta- and alpha-cell mass by different mechanisms according to the stage of development during which the treatment was applied. In fetuses exposed to glucocorticoids the last week of gestation only, beta-cell mass is reduced due to impairment of beta-cell commitment, whereas in fetuses exposed throughout gestation, islet vascularization and lower beta-cell proliferation are involved as well, amplifying the reduction of the endocrine mass.

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Glucocorticoids Inhibit Proliferation and Interleukin-4 and Interleukin-5 Secretion by Aeroallergen-Specific T-Helper Type 2 Cell Lines

Cited by 32 publications

References 32 publications

Non‐genomic rapid inhibition of Na⁺/H⁺‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

Non‐genomic rapid inhibition of Na⁺/H⁺‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

Comparison of the efficacy and safety of mometasone furoate dry powder inhaler to budesonide Turbuhaler

Impairment of Rat Fetal Beta-Cell Development by Maternal Exposure to Dexamethasone during Different Time-Windows

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Glucocorticoids Inhibit Proliferation and Interleukin-4 and Interleukin-5 Secretion by Aeroallergen-Specific T-Helper Type 2 Cell Lines

Cited by 32 publications

References 32 publications

Non‐genomic rapid inhibition of Na+/H+‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

Non‐genomic rapid inhibition of Na+/H+‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

Comparison of the efficacy and safety of mometasone furoate dry powder inhaler to budesonide Turbuhaler

Impairment of Rat Fetal Beta-Cell Development by Maternal Exposure to Dexamethasone during Different Time-Windows

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Non‐genomic rapid inhibition of Na⁺/H⁺‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

Non‐genomic rapid inhibition of Na⁺/H⁺‐exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids