Deficient glucocorticoid induction of anti-inflammatory genes in nasal polyp fibroblasts of asthmatic patients with and without aspirin intolerance

Fernández-Bertolín, Laura; Mullol, Joaquim; Fuentes, Mireya; Alobid, Isam; Roca‐Ferrer, Jordi; Picado, César; Pujols, Laura

doi:10.1016/j.jaci.2013.07.010

Cited by 6 publications

(14 citation statements)

References 14 publications

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“…The lack of data on the prevalence of GC resistance in CRS is due to the lack of a standardized clinical definition. While the asthma literature defines GC resistance in asthmatics as the failure to improve morning pre‐bronchodilator forced expiratory volume in 1 second (FEV1) values by greater than 15% of predicted value after 7 to 14 days of 20 mg of twice daily oral prednisone, no clinical definition of CRS GC resistance has been proposed despite a number of studies commenting on the presence of GC resistance in CRS.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis

Taylor

Schlosser

Soler

et al. 2018

Int Forum Allergy Rhinol

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis

Taylor

Schlosser

Soler

et al. 2018

Int Forum Allergy Rhinol

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“…Nasal fibroblasts respond to LPS via recognition of Toll-like receptors by producing inflammatory mediators such as the chemoattractants MCP-4, eotaxin and regulated on activation normal T cell expressed and secreted (RANTES), IL-6 and CXCL8, and growth factors such as the granulocyte/macrophage colony-stimulating factor (GM-CSF) [ 22 – 24 ]. We have previously reported that nasal polyp (NP) fibroblasts from patients with CRSwNP and asthma have a lower sensitivity to glucocorticoids, compared to nasal mucosa (NM) fibroblasts from control patients [ 21 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Lipopolysaccharide on Glucocorticoid Receptor Function in Control Nasal Mucosa Fibroblasts and in Fibroblasts from Patients with Chronic Rhinosinusitis with Nasal Polyps and Asthma

et al. 2015

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BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airways frequently associated with asthma. Bacterial infection is a feature of CRSwNP that can aggravate the disease and the response to glucocorticoid treatment.ObjectiveWe examined whether the bacterial product lipopolysaccharide (LPS) reduces glucocorticoid receptor (GR) function in control nasal mucosa (NM) fibroblasts and in nasal polyp (NP) fibroblasts from patients with CRSwNP and asthma.MethodsNP (n = 12) and NM fibroblasts (n = 10) were in vitro pre-incubated with LPS (24 hours) prior to the addition of dexamethasone. Cytokine/chemokine secretion was measured by ELISA and Cytometric Bead Array. GRα, GRβ, mitogen-activated protein-kinase phosphatase-1 (MKP-1) and glucocorticoid-induced leucine zipper (GILZ) expression was measured by RT-PCR and immunoblotting, GRα nuclear translocation by immunocytochemistry, and GRβ localization by immunoblotting. The role of MKP-1 and GILZ on dexamethasone-mediated cytokine inhibition was analyzed by small interfering RNA silencing.ResultsPre-incubation of nasal fibroblasts with LPS enhanced the secretion of IL-6, CXCL8, RANTES, and GM-CSF induced by FBS. FBS-induced CXCL8 secretion was higher in NP than in NM fibroblasts. LPS effects on IL-6 and CXCL8 were mediated via activation of p38α/β MAPK and IKK/NF-κB pathways. Additionally, LPS pre-incubation: 1) reduced dexamethasone’s capacity to inhibit FBS-induced IL-6, CXCL8 and RANTES, 2) reduced dexamethasone-induced GRα nuclear translocation (only in NM fibroblasts), 3) did not alter GRα/GRβ expression, 4) decreased GILZ expression, and 5) did not affect dexamethasone’s capacity to induce MKP-1 and GILZ expression. MKP-1 knockdown reduced dexamethasone’s capacity to suppress FBS-induced CXCL8 release.ConclusionThe bacterial product LPS negatively affects GR function in control NM and NP fibroblasts by interfering with the capacity of the activated receptor to inhibit the production of pro-inflammatory mediators. This study contributes to the understanding of how bacterial infection of the upper airways may limit the efficacy of glucocorticoid treatment.

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“…Nasal polyposis is a chronic inflammatory disease of the sinunasal mucosa frequently associated with asthma [19]. The infiltration of various inflammatory cells, epithelial damage and expression of the cytokines are similar to the pathological profile of asthma.…”

Section: Discussionmentioning

confidence: 99%

Does vitamin D have protective effect on human nasal polyposis: histological and immunohistochemical study

Faruk¹,

Yousef²,

Mohamed³

2014

J Histol Histopathol

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Background: Nasal polyps (NPs) are benign pedicled mucosal protrusions into the nasal cavity of multifactorial origin. Vitamin D has been demonstrated as having potential immunomodulatory activity and act as an antiproliferative agents. Aim of the work: To determine the possible antiproliferative effect and immunomodulatory activity of VD on human nasal polyposis. Material and methods: Based on thirty patients and divided equally into 3 groups. Group Ι (healthy subjects). Group ΙΙ were received low daily oral dose of VD(1000 IU) for 4 weeks. Group ΙΙΙ were received high daily oral dose of VD(4000 IU) for 4 weeks.Each group ΙΙ and ΙΙΙ divided into 2 subgroups; group b: patients with NP before taking VD and group a: patients with NP after taking. Nasal biopsies were obtained of all groups for histological examination and immunohistochemical detection of Toll-like receptors 9 expression. Results: patients of nasal polyps before VD taking (groups IIb and IIIb) presented with symptoms of Visual Analogue Scale, VAS score (facial pain, headache, nasal blockage, nasal discharge, post-nasal drip and olfactory disturbance) and endoscopic appearance of Lund and Mackey score (polypi, edema and discharge), damage of respiratory epithelium, extensive accumulation of collagen fibers in lamina propria and highly expressed TLR-9. The high dose VD group (IIIa) showed near normal respiratory epithelium, significant decrease (P<0.05) in all symptoms of VAS score, endoscopic appearance of Lund and Mackey score. The mean area % of submucosal accumulation of collagen fibers and TLR-9 expression were also significant decreased but decrease was insignificant (P<0.05) in the low dose VD group (IIa). Conclusion: VD participate significantly in protection against human nasal polyposis when used by high therapeutic dose, by reducing the size of nasal polyps, relieving the symptoms and signs of nasal polyposis.

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Deficient glucocorticoid induction of anti-inflammatory genes in nasal polyp fibroblasts of asthmatic patients with and without aspirin intolerance

Cited by 6 publications

References 14 publications

Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis

Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis

Effect of Lipopolysaccharide on Glucocorticoid Receptor Function in Control Nasal Mucosa Fibroblasts and in Fibroblasts from Patients with Chronic Rhinosinusitis with Nasal Polyps and Asthma

Does vitamin D have protective effect on human nasal polyposis: histological and immunohistochemical study

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