Overexpression of glucocorticoid receptor-β in severe allergic rhinitis

Ishida, Akihiro; Ohta, Nobuo; Koike, Shuji; Aoyagi, Masaru; Yamakawa, Mitsunori

doi:10.1016/j.anl.2009.12.002

Cited by 18 publications

(12 citation statements)

References 17 publications

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“…Examples of such genes included nuclear receptor subfamily 3, group C, ( NR3C1 ), which is also known as the glucocorticoid receptor, from the Glucocorticoid Receptor Signalling , which can be activated by glucocorticoids [33]. It has recently been reported that NR2C1 increased in nasal mucosal from patients with allergic rhinitis [34]. IL-21 receptor (IL-21R) from the T helper cell differentiation pathway is important in the development of Th2 response and has been demonstrated to be essential for allergic skin inflammation in humans and mice [35], [36].…”

Section: Discussionmentioning

confidence: 99%

Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4+ T Cells Are Reversed by Glucocorticoids

et al. 2012

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BackgroundGlucocorticoids (GCs) play a key role in the treatment of allergy. However, the genome-wide effects of GCs on gene expression in allergen-challenged CD4+ T cells have not been described. The aim of this study was to perform a genome-wide analysis to investigate whether allergen-induced gene expression changes in CD4+ T cells could be reversed by GCs.Methodology/Principal FindingsGene expression microarray analysis was performed to profile gene expression in diluent- (D), allergen- (A), and allergen + hydrocortisone- (T) challenged CD4+ T cells from patients with seasonal allergic rhinitis. Principal component analysis (PCA) showed good separation of the three groups. To identify the correlation between changes in gene expression in allergen-challenged CD4+ T cells before and after GC treatment, we performed orthogonal partial least squares discriminant analysis (OPLS-DA) followed by Pearson correlation analysis. This revealed that allergen-induced genes were widely reversed by GC treatment (r = −0.77, P<0.0001). We extracted 547 genes reversed by GC treatment from OPLS-DA models based on their high contribution to the discrimination and found that those genes belonged to several different inflammatory pathways including TNFR2 Signalling, Interferon Signalling, Glucocorticoid Receptor Signalling and T Helper Cell Differentiation. The results were supported by gene expression microarray analyses of two independent materials.Conclusions/SignificanceAllergen-induced gene expression changes in CD4+ T cells were reversed by treatment with glucocorticoids. The top allergen-induced genes that reversed by GC treatment belonged to several inflammatory pathways and genes of known or potential relevance for allergy.

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Section: Discussionmentioning

confidence: 99%

Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4+ T Cells Are Reversed by Glucocorticoids

et al. 2012

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“…Alternatively to the GR‐β mechanism, a decrease in GR‐α levels could attenuate the anti‐inflammatory actions of corticosteroids [18, 45]. The airway tissues from asthmatics had significantly lower GR‐α mRNA levels than those from normal individuals (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It is speculated that, in order to have a significant effect on GR‐α inhibition, GR‐β protein should be at least as abundant as GR‐α [51, 52]. Although the abundance of GR‐β mRNA has been reported to be much lower than GR‐α in several human tissues and cells, including PBMC, relative increases in GR‐β mRNA or protein have been consistently observed in the context of inflammatory diseases, which may be associated with glucocorticoid resistance [16–18, 20, 52, 53]. In the immortalized human bronchial epithelial cell line BEAS 2B, Pujols et al [47] reported that the relative abundance of GR‐β was 2800‐fold lower than the GR‐α messenger, which is even lower than the levels detected in the primary epithelial cells from this study (about 1500‐fold).…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of GR‐β in several transfected cell lines (COS‐1, CV‐1 and COS‐7) inhibited the trans‐repression activity of GR‐α on the activities of AP‐1 and NF‐κB [10, 11]. However, the generally lower relative abundance of GR‐β compared with that of GR‐α and its physiological significance are currently under debate [12–18].…”

Section: Introductionmentioning

confidence: 99%

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Induction of glucocorticoid receptor‐β expression in epithelial cells of asthmatic airways by T‐helper type 17 cytokines

Vazquez-Tello

Semlali

Chakir

et al. 2010

Clin Experimental Allergy

105

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“…Mediators like substance P have been associated with different symptoms in patients with AR as well as in nonallergic, noninfectious rhinitis . Similar to asthma, steroid resistance has been reported in AR and CRS and may be a reason for lack of control in both conditions. The mechanisms of steroid resistance in AR and CRS are far from being validated .…”

Section: Disease‐related Factors In Uncontrolled Upper Airway Symptomsmentioning

confidence: 98%

Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?

Hellings

Fokkens

Akdiş³

et al. 2012

Allergy

196

191

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State-of-the-art documents like ARIA and EPOS provide clinicians with evidence-based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so-called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline-directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment-related, diagnosis-related and/or patient-related factors. Treatment-related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom-oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient-related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.

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Overexpression of glucocorticoid receptor-β in severe allergic rhinitis

Cited by 18 publications

References 17 publications

Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4+ T Cells Are Reversed by Glucocorticoids

Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4+ T Cells Are Reversed by Glucocorticoids

Induction of glucocorticoid receptor‐β expression in epithelial cells of asthmatic airways by T‐helper type 17 cytokines

Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?

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