Dendritic Cell-Derived Tumor Necrosis Factor α Modifies Airway Epithelial Cell Responses

Lutfi, Riad; Ledford, John R.; Zhou, Ping; Lewkowich, Ian P.; Page, Kristen

doi:10.1159/000336984

Cited by 2 publications

(2 citation statements)

References 59 publications

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“…We have previously reported that a very early innate immune response occurred following allergen exposure. Within one hour, a significant release of TNFα in the BAL fluid is detected [13] and while this is maximal at 6 h post exposure, levels remain significantly higher than PBS controls up to 24 h later [7]. Neutrophil-derived TNFα production is important as we have shown that depletion of neutrophils prior to allergen exposure abolished GC frass-induced TNFα production when assessed 18 h later [7].…”

Section: Discussionmentioning

confidence: 99%

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The role of protease-activated receptor-2 on pulmonary neutrophils in the innate immune response to cockroach allergen

Lutfi¹,

Lewkowich

Zhou³

et al. 2012

J Inflamm

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BackgroundSerine proteases in German cockroach (GC) have been shown to mediate allergic airway inflammation through the activation of protease activated receptor (PAR)-2. Neutrophils play an important role in regulating the innate immune response, and are recruited into the airways following GC frass exposure. As such, we investigated the role of PAR-2 in airway neutrophil recruitment, activation and cytokine production following allergen exposure.MethodsWild type and PAR-2-deficient mice were administered a single intratracheal instillation of PBS or GC frass and neutrophil recruitment, expression of PAR-2, CD80, CD86, and MHC class II were assessed by flow cytometry and levels of tumor necrosis factor (TNF)α was assessed by ELISA. Uptake of AlexaFluor 405-labeled GC frass by neutrophils was performed by flow cytometry.ResultsNeutrophil recruitment in the lung and airways following GC frass exposure was significantly decreased in PAR-2-deficient mice compared to wild type mice. GC frass exposure increased the level of PAR-2 on pulmonary neutrophils and increased numbers of PAR-2-positive neutrophils were found in the lungs; however PAR-2 did not play a role in meditating allergen uptake. Comparing wild type and PAR-2-deficient mice, we found that a single exposure to GC frass increased levels of CD80 and CD86 on pulmonary neutrophils, an effect which was independent of PAR-2 expression. Neutrophils isolated from the whole lungs of naïve PAR-2-deficient mice treated ex vivo with GC frass produced significantly less TNFα than in similarly treated wild type neutrophils. Lastly, neutrophils were isolated from the bronchoalveolar lavage fluid of wild type and PAR-2-deficient mice following a single intratracheal exposure to GC frass. Airway neutrophils from PAR-2-deficient mice released substantially decreased levels of TNFα, suggesting a role for PAR-2 in neutrophil-derived cytokine production.ConclusionsTogether these data suggest PAR-2 expression can be upregulated on lung neutrophils following allergen exposure and the consequence is altered release of TNFα which could drive the early innate immune response.

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Section: Discussionmentioning

confidence: 99%

“…Many cells are likely involved in the initiation of the innate immune response, including the neutrophil, which we have consistently seen in high numbers following allergen exposure [7,10,13]. It is still unclear what the overall role of the neutrophil is in the initiation of allergic airway inflammation.…”

Section: Discussionmentioning

confidence: 99%

The role of protease-activated receptor-2 on pulmonary neutrophils in the innate immune response to cockroach allergen

Lutfi¹,

Lewkowich

Zhou³

et al. 2012

J Inflamm

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Role of Cockroach Proteases in Allergic Disease

Page

2012

Curr Allergy Asthma Rep

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Allergic asthma is on the rise in developed countries, and cockroach exposure is a major risk factor for the development of asthma. In recent years, a number of studies have investigated the importance of allergen-associated proteases in modulating allergic airway inflammation. Many of the studies have suggested the importance of allergen-associated proteases as having a direct role on airway epithelial cells and dendritic cells. In most cases, activation of the protease activated receptor (PAR)-2 has been implicated as a mechanism behind the potent allergenicity associated with cockroaches. In this review, we focus on recent evidence linking cockroach proteases to activation of a variety of cells important in allergic airway inflammation and the role of PAR-2 in this process. We will highlight recent data exploring the potential mechanisms involved in the biological effects of the allergen.

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Dendritic Cell-Derived Tumor Necrosis Factor α Modifies Airway Epithelial Cell Responses

Cited by 2 publications

References 59 publications

The role of protease-activated receptor-2 on pulmonary neutrophils in the innate immune response to cockroach allergen

The role of protease-activated receptor-2 on pulmonary neutrophils in the innate immune response to cockroach allergen

Role of Cockroach Proteases in Allergic Disease

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