The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

Gounni, Abdelilah Soussi

doi:10.1152/ajplung.00005.2006

Cited by 32 publications

(13 citation statements)

References 118 publications

(118 reference statements)

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“…[23][24][25][26][27][28] Upon re-exposure to the allergen and subsequent cross-linking of IgE via FcγRI, these cells are activated leading to the following phenomena: (1) mast cells and basophils are degranulated, releasing histamine and lipid mediators, which mediate immediate reactions, and cytokines (IL-4, IL-5, IL-13 and TNFα), which lead to late reactions (2) airway smooth muscle cell contraction is increased due to the markedly increased intracellular calcium concentration and secretion of Th2 cytokines (IL-4, IL-5, IL-13) and chemokines (eotacin-1CCL1) that are important for the perpetuation and modulation of airway inflammation 27,29 and (3) dendritic cells enhance antigen presentation to T cells, secrete several pro-inflammatory and chemotactic factors such as TNFα and MCP1, and skew towards a Th2-polarized response. 28 IgE upregulates the expression of FcγRI on these FcγRI bearing cells, leading to Th2 mediated inflammation and also mediates a significant survival effect on mast cells, neutrophils and monocytes through binding FcγRI.…”

Section: Introductionmentioning

confidence: 99%

Vaccines targeting IgE in the treatment of asthma and allergy

Peng

2009

Human Vaccines

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inappropriate immune responses characterized by the increase of serum IgE antibodies to common aeroallergens in genetically susceptible individuals.Serum IgE levels have been correlated with airway hyperresponsiveness both in adults 10,11 and in children, 12 and is associated with the severity of asthma. 13 It is well-established that the risk of developing asthma increases with increasing levels of serum IgE. 11 In addition to asthma, IgE is also responsible for allergic rhinitis, atopic dermatitis, adverse reactions to foods, medications, insect bites and stings and anaphylaxis, which are also increasing at an alarming rate. 3,5,14 Immunotherapies and biological agents in the treatment of asthma and allergy. Basic treatment for allergy and asthma includes (1) allergen avoidance, (2) pharmacological management that consists of sodium cromoglycate, inhaled corticosteroids, and histamine H1-receptor antagonists, etc. and (3) immunotherapy consisting of antigen-specific and non-allergen-specific approaches. 15 The purpose of antigen-specific immunotherapy is to desensitize allergic subjects by repeated subcutaneous injections of small and gradually increasing amounts of the offending allergen. This therapy has been used for more than 100 years and is effective in the treatment of hay fever and venom allergy, but is less effective in asthma control. 15 As most allergic subjects are sensitized to multiple allergens, non-allergen specific immunotherapy would be more effective in the treatment of these subjects. Overexpressed IgE and Th2 cytokines play important roles in the development of allergic inflammation; one intriguing strategy aims at limiting production of IgE and cytokines, or their accessibility to their respective receptors, so as to control the pathogenic process. To date, many new biological agents used as therapeutic modifiers have emerged as important new treatments. These include the administration of humanized monoclonal antibodies (mAbs) against such molecules or their receptors, soluble receptors, or mutated cytokines as passive blockers, [16][17][18][19] as summarised in Table 1. 16,20 Among these biological agents, the monoclonal antibody to IgE (omalizumab) has been proven to be effective in the treatment of asthma.IgE and its high affinity receptor (FcγRI). Since IgE was discovered in 1966, 21 it has been considered to be an important biological target in the treatment of allergy and asthma. IgE antibodies are known to play a major role in the development and regulation of asthmatic responses and are directly responsible for the allergic cascade. 22 These allergen-specific IgE antibodies bind to high affinity Allergic diseases including asthma are characterized by an increase of serum IgE levels. Since IgE was discovered in 1966, it has been considered to be the most important biological target in the treatment of allergy and asthma. Indeed, recent studies reveal that IgE, through its high affinity IgE receptors (FcεRI), is now considered a critical regulator of Th2 responses. This is suppor...

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Section: Introductionmentioning

confidence: 99%

Vaccines targeting IgE in the treatment of asthma and allergy

Peng

2009

Human Vaccines

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“…When administered in the airways, GCs may have several cellular targets that contribute to their therapeutic effectiveness in asthma management (2). Airway smooth muscle (ASM) has now been recognized as a novel player in the pathogenesis of asthma (3,4) and might therefore be expected to be a prominent therapeutic target for inhaled steroids (5). In line with this, we and others showed that GCs were effective in abrogating the expression of a number of pro-inflammatory mediators including cytokines, chemokines, and adhesion molecules in ASM cells (5)(6)(7)(8)(9)(10).…”

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confidence: 99%

Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells

Tliba¹,

Damera²,

Banerjee³

et al. 2008

Am J Respir Cell Mol Biol

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We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-a and IFN-g impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRb) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions could also be suppressed by short-term exposure of ASM cells to TNF-a and IFN-g (6 h) as shown by the abrogated glucocorticoid responsive element (GRE)-dependent gene transcription; surprisingly, neither GRa nuclear translocation nor GRb expression was affected by cytokine mixture. The earlier induction of CD38, a molecule recently involved in asthma, seen with TNF-a and IFN-g combination but not with cytokine alone, was also completely insensitive to steroid pretreatment. Chromatin-immunoprecipitation (IP) and siRNA strategies revealed not only increased binding of interferon regulatory factor 1 (IRF-1) transcription factor to CD38 promoter, but also its implication in regulating CD38 gene transcription. Interestingly, the capacity of fluticasone to completely inhibit TNF-a-induced IRF-1 expression, IRF-1 DNA binding, and transactivation activities was completely lost in cells exposed to TNF-a and IFN-g in combination. This early steroid dysfunction seen with cytokine combination could be reproduced by enhancing IRF-1 cellular levels using constitutively active IRF-1, which dose-dependently inhibited GRE-dependent gene transcription. Consistently, reducing IRF-1 cellular levels using siRNA approach significantly restored steroid transactivation activities. Collectively, our findings demonstrate for the first time that IRF-1 is a novel alternative GRb-independent mechanism mediating steroid dysfunction induced by pro-asthmatic cytokines, in part via the suppression of GRa activities.

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“…Although the longterm side effects of this therapy are yet unknown, alternative studies need to concentrate on the pro-inflammatory function of ASM. A myriad of articles showed that ASM is a target for and a source of different pro-asthmatic factors that could play a role, via autocrine and paracrine actions, in the orchestration and/or perpetuation of the chronic inflammatory process that occurs in the airways (1)(2)(3)(4)(5). This review will describe the clinical importance of interferon (IFN) signaling pathways in the regulation of the immunomodulatory functions of ASM.…”

mentioning

confidence: 99%

Airway Smooth Muscle Cell as an Inflammatory Cell: Lessons Learned from Interferon Signaling Pathways

Tliba¹,

Amrani²

2008

Proceedings of the American Thoracic Society

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The present article will describe the potential role of airway smooth muscle (ASM) in mediating both deleterious/beneficial effects of interferons (IFNs) in asthma. First described as beneficial in treating the main features of asthma, the interplay between IFNs and ASM could explain their deleterious actions recently described in a number of different studies. Through multiple mechanisms, including the suppression of steroid action, the synergistic pro-inflammatory actions when combined with other cytokines, and the modulation of calcium metabolism, IFNs are now seen as critical mediators in the pathogenesis of asthma.

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The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

Abstract: Gounni, Abdelilah Soussi. The high-affinity IgE receptor (Fc⑀RI): a critical regulator of airway smooth muscle cells? Am

Cited by 32 publications

References 118 publications

Vaccines targeting IgE in the treatment of asthma and allergy

Vaccines targeting IgE in the treatment of asthma and allergy

Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells

Airway Smooth Muscle Cell as an Inflammatory Cell: Lessons Learned from Interferon Signaling Pathways

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