Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

Díaz, Patricia; Pinto, Ricardo A.; Mamani, Rossana; Uasapud, Paola; Bono, Marı́a Rosa; Gaggero, Aldo; Guerrero, Julia; Goecke, Annelise

doi:10.1542/peds.2012-0160

Cited by 27 publications

(29 citation statements)

References 27 publications

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“…Mean IFN‐β ( IFNB ) and IFN‐γ ( IFNG ) mRNA expression was not significantly different between panels. Cytokines interleukin 6 (IL‐6) and tumor necrosis factor α (TNF‐α) have also been implicated in response to RSV (30), but mean mRNA expression did not differ between panels (data not shown). However, a significant inverse correlation was found between RSV‐g expression and IL‐6 expression among all LCLs at48 hpi ( Fig.…”

Section: Resultsmentioning

confidence: 99%

A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection

et al. 2014

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Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infection during childhood and causes severe symptoms in some patients, which may cause hospitalization and death. Mechanisms for differential responses to RSV are unknown. Our objective was to develop an in vitro model of RSV infection to evaluate interindividual variation in response to RSV and identify susceptibility genes. Populations of human-derived HapMap lymphoblastoid cell lines (LCLs) were infected with RSV. Compared with controls, RSV-G mRNA expression varied from ~1- to 400-fold between LCLs. Basal expression of a number of gene transcripts, including myxovirus (influenza virus) resistance 1 (MX1), significantly correlated with RSV-G expression in HapMap LCLs. Individuals in a case-control population of RSV-infected children who were homozygous (n=94) or heterozygous (n=172) for the predicted deleterious A allele in a missense G/A SNP in MX1 had significantly greater risk for developing severe RSV disease relative to those with the major allele (n=108) (χ(2)=5.305, P=0.021; OR: 1.750, 95% CI: 1.110, 2.758, P=0.021). We conclude that genetically diverse human LCLs enable identification of susceptibility genes (e.g., MX1) for RSV disease severity in children, providing insight for disease risk.

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Section: Resultsmentioning

confidence: 99%

A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection

et al. 2014

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“…In the last years, data on GCR expression and critical illness in humans have started evolving and many groups have described glucocorticoid resistance in cohorts of septic patients. Results of these studies have shown lower GCR‐α and increased GCR‐β expression levels in septic patients compared to healthy subjects, and decreased α:β GCR ratio and increased GCR‐β expression were shown to be related to illness severity in infants with bronchiolitis . Another study showed that total and cytoplasmic, but not nuclear GCR levels, were significantly lower in critically ill children compared to healthy controls .…”

Section: Discussionmentioning

confidence: 99%

Decreased glucocorticoid receptor expression during critical illness

Vassiliou

Floros

Jahaj

et al. 2019

Eur J Clin Investigation

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Introduction In critically ill patients, the hypothalamic‐pituitary‐adrenal axis is activated, resulting in increased serum cortisol concentrations. However, in some patients, especially those with sepsis, cortisol levels are relatively low for the degree of illness severity. Therefore, in the present project, we aim to characterize the time course of glucocorticoid receptor (GCR) alpha and beta expression in peripheral polymorphonuclear cells of critically ill septic or nonseptic patients using real‐time PCR. Design A prospective observational study conducted on 32 critically ill adults not receiving steroids, in a university‐affiliated, multidisciplinary intensive care unit (ICU). Blood samples were collected for measurement of glucocorticoid receptor expression within 24‐48 hours of admission to the ICU and at days 4, 8 and 13 after admission, reflecting the acute and chronic phase of the illness. Results During ICU stay, patients expressed over time reduced levels of both GCR‐α and GCR‐β mRNA. More specifically, GCR‐α mRNA expression was decreased fourfold 4 days after admission (P < 0.0001) and remained low up to 2 weeks after admission (P < 0.001). On the other hand, GCR‐β mRNA levels remained stable shortly after admission, but approx. one week after admission, its levels decreased threefold (P < 0.01) and remained reduced up to 2 weeks after admission (P < 0.001). Discussion Our results suggest that critically ill patients have highly variable expression of alpha and beta GCR, and moreover, the levels of both receptors decrease during ICU stay. Taken together, these might explain the differential responsiveness of patients to exogenous steroid administration or to endogenous cortisol secretion.

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“…Recientemente, Hinsey y col 35 publicaron que en células de cultivo había una inhibición directa del VRS en la acción antiinflamatoria de los corticoides. En los lactantes estudiados por nosotros, encontramos, en relación a la gravedad del paciente, un aumento del receptor de glucocorticoides beta (GR-β) que es inactivo en la respuesta a corticoides 36 . Esto podría explicar en parte, que el cortisol no tenga una acción antiinflamatoria en un subgrupo de pacientes que presenta una evolución de gravedad.…”

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Aumento de interleuquinas proinflamatorias y de cortisol plasmático en bronquiolitis por virus respiratorio sincicial: relación con la gravedad de la infección

et al. 2013

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Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

Abstract: The decrease of the α:β GR ratio by an increase of β receptors expression is related to illness severity and may partly explain the insensitivity to corticoid treatment in RSV-infected infants. The increased expression of β GR could be a marker of disease severity.

Cited by 27 publications

References 27 publications

A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection

A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection

Decreased glucocorticoid receptor expression during critical illness

Aumento de interleuquinas proinflamatorias y de cortisol plasmático en bronquiolitis por virus respiratorio sincicial: relación con la gravedad de la infección

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