Structural Cell-Derived Cytokines in Allergic Inflammation

Denburg, Judah A.; Gauldie, Jack; Dolovich, J.; Ohtoshi, Takayuki; Cox, Gerard; Jordana, Manel

doi:10.1159/000235343

Cited by 50 publications

(18 citation statements)

References 19 publications

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“…Thus, the impact of salbutamol on cellular responses can vary substantially with the system employed. The authors assessed its impact in vivo under clinical experimental conditions and found that the sputum eosinophils, and most likely some lung structural cell populations [23,37,41], strongly expressed CXCL8/IL-8. Unlike structural cells, the eosinophils would have infiltrated the lungs in response to the allergen challenge [5] 16-20 h following the last dose of salbutamol, so they may not have been directly exposed to substantial concentrations of this agonist.…”

Section: Discussionmentioning

confidence: 99%

Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response

Gordon

Swystun²,

Li³

et al. 2003

Eur Respir J

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Regular salbutamol use can exacerbate allergen-induced airway eosinophilia in asthmatics, but its effect on airway eosinophil chemokine responses is unknown.Asthmatic subjects (n=14) were treated for 10 days with placebo or salbutamol in a double-blind, cross-over study, then given same-dose allergen challenges. Their sputa were then analysed 1 and 7 h later for a panel of eosinophil-related cytokines. Eosinophils from five test and three control subjects were tested for expression of CXCL8/interleukin (IL)-8, and its receptors and responsiveness to CCL11/eotaxin and CXCL8/IL-8.Sputum CXCL8/IL-8, but not IL-5, CCL5/regulated on activation, T-cell expressed and secreted, CCL7/monocyte chemotactic protein-3, CCL11/eotaxin, granulocytemacrophage colony-stimulating factor or tumour necrosis factor levels, were increased (42%) by the salbutamol treatments. The CXCL8/IL-8 levels correlated with the proportions of sputum eosinophils and these cells, but not other sputum cells, stained strongly for CXCL8/IL-8. The circulating eosinophils of the tested subjects (n=5) expressed CXCL8/IL-8 receptors and secreted high levels of this chemokine. Neutralisation of sputum CXCL8/IL-8 reduced eosinophil chemotactic responses to these samples by 19¡5%.These data suggest that regular use of salbutamol can augment airway CXCL8/ interleukin-8 responses to allergen challenge and that this CXCL8/interleukin-8 could contribute to the airway inflammatory response. Eur Respir J 2003; 22: 118-126 Inhaled b 2 -adrenergic receptor agonists (b 2 -agonists) comprise a primary therapy for bronchoconstriction in allergic asthma patients. However, evidence suggests that regular use of b 2 -agonists can reduce their effectiveness [1, 2] and lead to increased airway hyperresponsiveness [3][4][5] and eosinophil/ mast cell responses [4,5] to allergen challenge. Given the association of eosinophils with asthma severity and pathology [6], the cellular mechanisms that may regulate this eosinophil response were questioned.Eosinophils express receptors for many molecules that are highly pertinent to asthma pathophysiology [6]. For example, the CCR3 receptor, which binds multiple CC chemokines (e.g. CCL11/eotaxin [6]), is broadly accepted as critical to the eosinophil response. However, CXCL8/interleukin (IL)-8 is also strongly expressed within allergic lesions [7][8][9][10] and eosinophils are responsive to this CXCR1/CXCR2 ligand [11,12]. Indeed, the decreased eosinophilia after allergen immunotherapy may be related to reduced CXCL8/IL-8 responses to allergen challenge [13].In a recent study in which mildly asthmatic subjects (n=14) regularly used salbutamol (or placebo) for 10 days, an exacerbation of asthmatic responses (forced expiratory volume in one second (FEV1), serum tryptase and sputum eosinophils) to allergen challenge was observed [5]. In order to gain insight into potential mechanisms behind this eosinophilia [4,5], a panel of nine pertinent eosinophil-signalling cytokines/ chemokines in sputum, previously obtained from these subjec...

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Section: Discussionmentioning

confidence: 99%

Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response

Gordon

Swystun²,

Li³

et al. 2003

Eur Respir J

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“…In addition to their fibrotic potential, fibroblasts release other mediators that are important in the pathogenesis of asthma (11)(12)(13). For instance, fibroblasts are an important source of eotaxin, a potent eosinophil chemoattractant (13,14).…”

mentioning

confidence: 99%

Regional Fibroblast Heterogeneity in the Lung

Kotaru

Schoonover²,

Trudeau³

et al. 2006

Am J Respir Crit Care Med

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Rationale: Excessive deposition of extracellular matrix occurs in proximal airways of individuals with asthma, but fibrosis in distal lung has not been observed. Whether differing fibrotic capacities of fibroblasts from these two regions contribute to this variability is unknown. Objectives: We compared morphologic and functional characteristics of fibroblasts isolated from proximal airways and distal lung parenchyma to determine phenotypic differences. Methods: Concurrent proximal airway and distal lung biopsies were obtained by bronchoscopy from subjects with asthma to isolate airway and distal lung fibroblasts, respectively. The following characteristics were compared: morphology, proliferation, ␣-smooth muscle actin expression, and synthesis of procollagen type I and eotaxin-1. Results: Airway fibroblasts (AFs) are morphologically distinct from distal lung fibroblasts (DLFs): they are larger (2.3-fold greater surface area vs. matched DLFs; p ϭ 0.02), stellate in appearance, and with more cytoplasmic projections compared with the spindleshaped DLFs. AFs synthesized more procollagen type I than did DLFs at baseline (twofold higher; p ϭ 0.003) and after transforming growth factor-␤ stimulation (1.4-fold higher; p ϭ 0.02). Similarly, AFs produced more eotaxin-1 than did DLFs at baseline (2.5-fold higher; p ϭ 0.004) and after interleukin-13 stimulation (13-fold higher; p ϭ 0.0001). In contrast, DLFs proliferate more than AFs with serum stimulation (about sixfold greater; p ϭ 0.03). Unstimulated DLFs also expressed more ␣-smooth muscle actin than did corresponding AFs (p ϭ 0.006). Conclusions: These studies suggest that at least two phenotypes of fibroblast exist in the lung. These phenotypic differences may partially explain the variable responses to injury and repair between proximal airways and distal lung/parenchyma in asthma and other respiratory diseases.

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“…However, the technique still awaits standardisation before its usefulness in measuring airway inflammation can be fully validated. eosinophils, basophils, macrophages/monocytes and epithelial cells [24][25][26][27].…”

Section: Methods Used To Investigate Cytokine Expression In Children mentioning

confidence: 99%

T Cell Cytokine Production in Childhood Asthma

Brown¹,

Ennis

2005

CRMR

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A recent asthma audit demonstrated that, 1.4 million children (one in eight) in the UK today are receiving treatment for their asthma, and that this figure has increased six-fold in the last 25 years. The chronicity of asthma has been associated with cytokine-mediated inflammation, in particular from T helper 1 (Th1) and T helper 2 (Th2) cells. Over the past 10 years, a number of studies have tried to unravel the role of T cell cytokines in childhood asthma, as there may well be differences between childhood and adult asthma. Research in this area has been hampered by ethical and practical difficulties. Although a number of studies use whole or separated blood for investigative purposes, the use of T cells obtained from the airways, obtained by bronchoalveolar lavage (BAL), or sputum may be more representative of in vivo cytokine expression. A large body of evidence suggests, that Th2 cytokines are upregulated in paediatric asthma. However, a number of more recent publications propose that Th1 cytokines may also have inflammatory effects in childhood asthma. In particular, IFNγ's role in childhood asthma has been clearly documented in studies, from both blood and BAL. Such reports have questioned the concept of the Th1/Th2 imbalance in such childhood asthma. This review will discuss the current findings on cytokine production from T cells in children with atopic asthma, and attempt to unravel the cytokine complexities in childhood asthma.

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Structural Cell-Derived Cytokines in Allergic Inflammation

Cited by 50 publications

References 19 publications

Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response

Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response

Regional Fibroblast Heterogeneity in the Lung

T Cell Cytokine Production in Childhood Asthma

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