Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine

Barczyk, Adam; Pierzchała, Władysław; Sozańska, Ewa

doi:10.1053/rmed.2003.1507

Cited by 322 publications

(258 citation statements)

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“…[32][33][34][35][36] IL-17A also plays a role in human asthmatic patients and in airways of allergic animals. 18,28,30,[37][38][39] Studies have found that in patients with moderate-to-severe asthma, neutrophils are found to be more abundant than eosinophils in the bronchoalveolar lavage fluid. 30,31,40 IL-17A can promote neutrophil recruitment, which might contribute to certain asthmatic phenotypes characterized by both high neutrophil counts and IL-17A expression.…”

Section: Discussionmentioning

confidence: 99%

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

Huang

Wachi

Thai

et al. 2008

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 99%

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

Huang

Wachi

Thai

et al. 2008

Journal of Allergy and Clinical Immunology

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“…More importantly, in humans increased expression of IL-17A and IL-17F has been shown in bronchial submucosa of moderate to severe asthma, and the evaluation of induced sputum in patients with asthma revealed that neutrophilic inflammation was frequently present, particularly in the severe forms of disease (75,79,80). Furthermore, it has been reported that increased AHR in response to methacholine in patients with asthma positively correlates with IL-17A levels in the sputum (81). Finally, a polymorphism in IL-17F that results in a loss-of-function mutation is inversely related to asthma risk (82).…”

Section: Th17 Lymphocytes and Asthmamentioning

confidence: 99%

Th17 cells: new players in asthma pathogenesis

Cosmi

Liotta

Maggi

et al. 2011

Allergy

288

198

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CD4+ T effector lymphocytes are distinguished in different subsets on the basis of their patterns of cytokine secretion. Th1 cells, thank to IFN-c production, are responsible for cell-mediated immunity against intracellular pathogens, Th2 cells, through the production of IL-4, provide some degree of protection against helminthes, and Th17 cells, via IL-17, promote neutrophils recruitment for the clearance of bacteria and fungi. However, beyond their protective role, these T-helper subsets can also be involved in the pathogenesis of several inflammatory diseases. Asthma is an inflammatory disease characterized by different clinical phenotypes. Allergic asthma is the result of an inflammatory process driven by allergen-specific Th2 lymphocytes, whereas Th17 cells are mainly involved in those forms of asthma, where neutrophils more than eosinophils, contribute to the inflammation. The identification in allergic asthma of Th17/Th2 cells, able to produce both IL-4 and IL-17, is in keeping with the observation that different clinical phenotypes can coexist in the same patient. In conclusion, a picture in which different T-cell subpopulations are active in different phase of bronchial asthma is emerging, and the wide spectrum of clinical phenotypes is probably the expression of different cellular characters playing a role in lung inflammation.

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“…Inactivation of protease activity led to reduction in allergic parameters. These results demonstrate that proteolytic activity of Per a 10 potentiates its allergenicity.There was an increase in levels of IL-17A in the sputum of severe asthmatics [23] and may act as a marker and risk factor for severe asthma [24]. Previously, it was shown that GC frass induces IL-17A secretion in a PAR-2-dependent manner.…”

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confidence: 91%

Protease activity of Per a 10 potentiates Th2 polarization by increasing IL‐23 and OX40L

2015

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Proteases are implicated in exacerbation of allergic diseases. In this study, the role of proteolytic activity of Per a 10 was evaluated on Th2 polarization. Intranasal administration of Per a 10 in mice led to allergic airway inflammation as seen by higher IgE levels, cellular infiltration, IL-17A, and Th2 cytokines, whereas, inactive ( )Per a 10 showed attenuated response. There was an increased OX40L expression on lung and lymph node dendritic cells in Per a 10 immunized group and on Per a 10 stimulated BMDCs. Reduction in CD40 expression without any change at transcript level in lungs of Per a 10 immunized mice suggested CD40 cleavage. BMDCs pulsed with Per a 10 showed reduced CD40 expression with lower IL-12p70 secretion as compared to heat inactivated Per a 10. IL-23, TNF-α, and IL-6 levels were significantly higher in Per a 10 stimulated BMDCs supernatant. In DC-T cell coculture studies, Per a 10 pulsed BMDCs showed higher levels of IL-4 and IL-13 that were reduced on blocking of either IL-23 or OX40L. In conclusion, the data suggests a critical role of protease activity of Per a 10 in promoting Th2 polarization by increasing IL-23 secretion and OX40L expression on dendritic cells.Keywords: CD40 r Cytokines r Dendritic cell r OX40L r Protease allergen Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionProteases are known to play an important role in manifestation of diseases like cancer, coagulopathies, respiratory inflammatory diseases, rheumatoid arthritis, and degenerative diseases [1][2][3]. Proteases from sources like house dust mite (Der p 1, Der p 3, Der p 6, Der p 9, Der f 1) and fungi (Asp f 13, Pen c 1, Pen c 13, Epi p 1) have been characterized as potent allergens [4]. Protease allergens act by proteolytic cleavage of an array of cell surface molecules and are known to modulate the functions of a variety of cell types including both immune and structural cells [5]. Proteolytic allergens from house dust mite are known to exacerbate allergic immune responses by selective cleavage of CD23, CD25, DC-SIGN, and DC-SIGNR on surface of immune cells Correspondence: Dr. Naveen Arora e-mail: naveen@igib.res.in; navdelhi@hotmail.com [6,7]. Further, cleavage and subsequent activation of PAR receptors by proteases lead to increased secretion of chemokines, proinflammatory, and pro Th2 cytokines from airway epithelial cells [8,9]. Studies have reported impaired epithelial barrier function as the feature of allergic diseases like asthma and atopic dermatitis [10]. The enzymatic activity of proteases has been reported to compromise epithelial barrier directly by cleaving tight junction proteins ZO-1 and occludin thereby increasing epithelial permeability [11,12]. Proteases can also act as adjuvants to bystander allergens present in the same microenvironment [13,14].Cockroaches have emerged as an important source of indoor allergens worldwide and cockroach extract is shown to be rich in proteases [15]. Previously, Per a 10, a serine protea...

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Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine

Abstract: According to our results IL-17 is probably not involved in pathogenesis of stable COPD, but it may play a role in people with airway hyperresponsiveness.

Cited by 322 publications

References 34 publications

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

Th17 cells: new players in asthma pathogenesis

Protease activity of Per a 10 potentiates Th2 polarization by increasing IL‐23 and OX40L

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