Important research questions in allergy and related diseases: 3‐chronic rhinosinusitis and nasal polyposis – a GA<sup>2</sup>LEN study

Bachert, Claus; Bruaene, Nicholas Van; Toskala, Elina; Zhang, N.; Olze, Heidi; Scadding, Glenis; Drunen, Cornelis M. van; Mullol, Joaquim; Cardell, Lars Olaf; Gevaert, Philippe; Zele, Thibaut Van; Claeys, Sofie; Halldén, Christer; Kostamo, Katriina; Foerster, Ulrike; Kowalski, Marek L.; Bieniek, Katarzyna; Olszewska-Ziąber, A; Niżankowska‐Mogilnicka, Ewa; Szczeklik, Andrzej; Świerczyńska, Monika; Arcimowicz, Magdalena; Lund, Valerie J.; Fokkens, Wytske J.; Zuberbier, Torsten; Akdiş, Cezmi A.; Canonica, Giorgio Walter; Cauwenberge, Paul Van; Burney, Peter; Bousquet, Jean

doi:10.1111/j.1398-9995.2009.01964.x

Cited by 108 publications

(97 citation statements)

References 137 publications

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“…Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease of the sinus mucosa characterized by both tissue inflammation and remodeling (Bachert et al, 2009). Nasal polyps reveal frequent epithelial damage, a thickened basement membrane, and an edematous stroma with abundant infiltration of inflammatory cells, predominantly activated eosinophils, and fibrotic foci.…”

Section: Introductionmentioning

confidence: 99%

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Pujols

Fernández-Bertolín²,

Fuentes³

et al. 2012

J Pharmacol Exp Ther

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Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflammatory and antifibrotic effects on animal models of various inflammatory and fibrotic diseases. Their effects in cells from patients affected by either inflammatory or fibrotic diseases have been poorly investigated. Nasal polyposis is a chronic inflammatory disease of the sinus mucosa characterized by tissue inflammation and remodeling. We tested the hypothesis that proteasome inhibition of nasal polyp fibroblasts might reduce their proliferation and inflammatory and fibrotic response. Accordingly, we investigated the effect of the proteasome inhibitor Z-Leu-Leu-Leu-B(OH) 2 (MG262) on cell viability and proliferation and on the production of collagen and inflammatory cytokines in nasal polyp and nasal mucosa fibroblasts obtained from surgery specimens. MG262 reduced the viability of nasal mucosa and polyp fibroblasts concentration-and time-dependently, with marked effects after 48 h of treatment. The proteasome inhibitor bortezomib provoked a similar effect. MG262-induced cell death involved loss of mitochondrial membrane potential, caspase-3 and poly(ADP-ribose) polymerase activation, induction of c-Jun phosphorylation, and mitogen-activated protein kinase phosphatase-1 expression. Low concentrations of MG262 provoked growth arrest, inhibited DNA replication and retinoblastoma phosphorylation, and increased expression of the cell cycle inhibitors p21 and p27. MG262 concentrationdependently inhibited basal and transforming growth factor-␤-induced collagen mRNA expression and interleukin (IL)-1␤-induced production of IL-6, IL-8, monocyte chemoattractant protein-1, regulated on activation normal T cell expressed and secreted, and granulocyte/macrophage colony-stimulating factor in both fibroblast types. MG262 inhibited IL-1␤/tumor necrosis factor-␣-induced activation of nuclear factor-B. We conclude that noncytotoxic treatment with MG262 reduces the proliferative, fibrotic, and inflammatory response of nasal fibroblasts, whereas high MG262 concentrations induce apoptosis.

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Section: Introductionmentioning

confidence: 99%

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Pujols

Fernández-Bertolín²,

Fuentes³

et al. 2012

J Pharmacol Exp Ther

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“…Once on the nasal mucosa, the circulating cells will promote tissue damage 8,[10][11][12] . Bachert et al 2 stated that deregulation of chemokines and adhesion molecules production might be important in promoting the local chemotaxis of eosinophils.…”

Section: Introductionmentioning

confidence: 99%

“…Nasal polyps (NP) is an inflammatory disease, which primarily affects the sinonasal mucosa 1,2 . Inflammation is generally induced by pro-inflammatory cytokines, such as TNF-α (tumor necrosis factor-α) and IL-1β (interleukin-1β) and mediated by transcriptional factors (TF), such as NF-κβ (nuclear factor-κβ) and AP-1 (activator protein-1) 3 .…”

Section: Introductionmentioning

confidence: 99%

In vitro effect of glucocorticoids on nasal polyps

Valera¹,

Brassesco²,

Castro‐Gamero³

et al. 2011

Braz. j. otorhinolaryngol. (Impr.)

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Glucocorticoids are considered the main treatment option for nasal polyps, but their effect is only recently being understood. Aim To evaluate whether fluticasone propionate (FP) inhibits the inflammatory process induced by TNF-alpha in vitro , and to assess if NF-kappaB is associated to this inhibition. Study Design Experimental in vitro study. Materials and Methods Nasal polyp fibroblasts were cultured during 24 hours. Three different concentrations of FP (1, 10 and 100 nM, added to TNF-alpha) were compared to negative (without additive) and positive (TNF-alpha) controls. Gene expression (RTQ-PCR) and protein concentration (ELISA) of VCAM-1, ICAM-1, eotaxin and RANTES were measured, as well as the nuclear translocation of NF-kappaB. Results TNF-alpha significantly increased protein concentration and RNA expression of all the studied molecules, as well as the nuclear translocation of NF-kappaB, when compared to the negative control. FP decreased these parameters in a dose-dependent manner, statistically different from positive control up to 100nM. Conclusions FP extensively inhibited inflammatory recruiters, at both protein and RNA levels, confirming the ability of glucocorticoids to modulate the inflammatory process in nasal polyps. This inhibition was associated to decreased NF-kappaB nuclear translocation, demonstrating that this is an important mechanism of glucocorticoids action for nasal polyps.

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“…However, allergy is not the only mechanism involved [14,15,16,17]. The present document will propose the definition of the severity of allergic and related (nonallergic origin) diseases: asthma, rhinitis (conjunctivitis), rhinosinusitis [18,19,20], atopic dermatitis (AD) and chronic urticaria [21,22]. Occupational diseases will not be considered in this document.…”

Section: Introductionmentioning

confidence: 99%

Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA<sup>2</sup>LEN – ARIA Position Paper

Bousquet¹,

Antó²,

Demoly³

et al. 2012

Int Arch Allergy Immunol

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Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

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Important research questions in allergy and related diseases: 3‐chronic rhinosinusitis and nasal polyposis – a GA²LEN study

Cited by 108 publications

References 137 publications

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

In vitro effect of glucocorticoids on nasal polyps

Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA<sup>2</sup>LEN – ARIA Position Paper

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Important research questions in allergy and related diseases: 3‐chronic rhinosinusitis and nasal polyposis – a GA2LEN study

Cited by 108 publications

References 137 publications

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

In vitro effect of glucocorticoids on nasal polyps

Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA<sup>2</sup>LEN – ARIA Position Paper

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Important research questions in allergy and related diseases: 3‐chronic rhinosinusitis and nasal polyposis – a GA²LEN study