The paradigm of cytokine networks in allergic airway inflammation

Pawankar, Ruby; Hayashi, Miyuki; Yamanishi, Shingo; Igarashi, Toru

doi:10.1097/aci.0000000000000129

Cited by 61 publications

(51 citation statements)

References 69 publications

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“…The pro-inflammatory cytokine IL-6 is one of the key biomarkers in both ARDS patients and animal models that can predict the morbidity and mortality of ARDS patients [30, 31]. IFN-γ, a Th1 associated pro-inflammatory cytokine, is known to be essential in airway inflammation and inducing the influx of neutrophils [32, 33]. As a major inducer of CXCL10, excessive production of IFN-γ and CXCL10 contributed to injury progression in ARDS [34].…”

Section: Discussionmentioning

confidence: 99%

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats

Lang

Wang

et al. 2017

PLoS ONE

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The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

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Section: Discussionmentioning

confidence: 99%

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats

Lang

Wang

et al. 2017

PLoS ONE

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“…The defining features of asthma are inflammation, airway hyperresponsiveness, reversible airway obstruction, and airway structural remodeling [3, 4]. A large array of cytokines, chemokines, and other pro-inflammatory mediators released by both immune-inflammatory and airway structural cells contribute to the pathophysiology asthma [5–7]. Considerable evidence shows that airway inflammation is a major factor in asthma pathogenesis, and that bronchial hyperresponsiveness in asthma often correlates with disease severity [8].…”

Section: Introductionmentioning

confidence: 99%

Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma

Wang

Gao

et al. 2016

Respir Res

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BackgroundSteroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics.MethodsAdults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment. Blood samples were collected from all patients during their first visit of the study. Neutrophils isolated from the blood were cultured with dexamethasone and/or atopic asthmatic serum for 18 h. The mRNA expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), a glucocorticoid transactivation target, and glucocorticoid-induced transcript 1 (GLCCI1), an early marker of glucocorticoid-induced apoptosis whose expression was associated with the response to inhaled glucocorticoids in asthma , was determined by real-time PCR, and ELISA was used to assess the pro-inflammatory cytokine IL-8 levels in the supernatant. Constitutive neutrophil apoptosis was detected by flow cytometry.ResultsDEX significantly induced MKP-1 expression in both patients with SS and SR patients in a concentration-dependent manner, but greater induction was observed for SS patients at a low concentration (10−6 M). Asthmatic serum alone showed no MKP-1expression, and there was impaired induction of MKP-1 by DEX in SR asthma patients. The expression of GLCCI1 was not induced in neutrophils with DEX or DEX/atopic asthmatic serum combination. Greater inhibition of IL-8 production was observed in neutrophils from patients with SS asthma treated with DEX/atopic asthmatic serum combination compared with SR asthma patients, though DEX alone showed the same effect on neutrophils from SS and SR asthma patients. Meanwhile, DEX dependent inhibition of constitutive neutrophil apoptosis was similar between SS asthma and SR asthma patients.ConclusionsDEX exerted different effects on neutrophils from patients with SS asthma and SR asthma, which may contribute to glucocorticoid insensitivity.

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“…These molecules operate upstream of the canonical T H 2 cytokines, primarily IL-4, IL-5, and IL-13, which play a pivotal role in allergy ( Figure 1) [15]. At the mucosal surface, the triad of AECderived cytokines are important regulators of maintenance of immune homeostasis and induction of both a protective and an inflammatory T H 2-type immune response [16][17][18]. Dysregulation of these cytokines can lead to exacerbated recruitment and activation of specific immune cells, such as dendritic cells (DCs), type-2 innate lymphoid cells (ILC2s), mast cells (MCs), eosinophils, neutrophils, and basophils, and thus promote a long-term T H 2-type airway hyperresponsiveness spiral.…”

Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease. Key words: Airway epithelium. Barrier dysfunction. Respiratory allergy. Redox biology. Air pollutants. ResumenEl epitelio pulmonar constituye la barrera celular más susceptible a la acción deletérea de la multitud de agentes que se encuentran en el ambiente, incluidos los alérgenos. Además de prevenir su acceso al organismo, la barrera epitelial de las vías respiratorias juega un papel inmunomodulador crucial, regulando de forma local la acción de las células del sistema inmune subyacentes. Una disfunción epitelial, provocada tanto directa como indirectamente por la acción de los aeroalérgenos, parece ser una de las causas principales de desregulación de la homeostasis pulmonar, causando una respuesta proinflamatoria descontrolada que cada vez más autores atribuyen al origen de las reacciones alérgicas. En esta revisión se quiere destacar el papel de la barrera epitelial pulmonar como regulador de la respuesta inmune en el contexto de la alergia. Las enfermedades crónicas que afectan a las vías respiratorias, tales como el asma alérgica, muestran frecuentemente una función epitelial defectuosa, apoyando así la hipótesis antes mencionada que subyace al origen de la alergia. El impacto de otros contaminantes ambientales -como virus respiratorios, bacterias, humo del tabaco y partículas diésel-sobre la integridad epitelial, así como su influencia en la biología redox pulmonar relacionada con el desarrollo de la respuesta alérgica, también se abordarán en la presente revisión.

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The paradigm of cytokine networks in allergic airway inflammation

Abstract: A new paradigm of an interplay of cytokines is important in allergic rhinitis and asthma in orchestrating the allergic inflammatory response. Potential therapeutic applications emerging from the roles of these cytokines are promising, but need further research.

Cited by 61 publications

References 69 publications

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats

Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

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