β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells

Abstract

BackgroundLong-acting β2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports suggest that LABAs have an anti-inflammatory effect in bronchial asthma, and this should be further investigated. The aim of this study was to investigate whether LABAs inhibit allergic airway inflammation and how this occurs.ResultsWe assessed the effect of the LABA formoterol (FORM) on inflammatory cell responses in airway, lung and regional lymph nodes, using an HDM-induced murine allergic asthma model in vivo. The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro. Adoptive transfer of BMDCs pulsed with HDM in the presence or absence of FORM to naïve mice was performed and the inflammatory response to subsequent HDM challenge was analyzed. FORM treatment suppressed HDM-induced changes and caused an increase in the number of eosinophils and neutrophils in bronchoalveolar lavage. The concentration of IL-4 and IL-17 in lung tissue homogenate was elevated and led to an accumulation of IL-4, IL-13, IL-5 and IL-17 producing cells in regional lymph nodes. FORM inhibited the production of IL-6 and IL-23 from BMDCs stimulated with HDM in vitro, and enhanced IL-10 production. The BMDCs adoptive transfer experiment indicated that dendritic cells mediate the effect of FORM, since FORM treatment of BMDCs in vitro attenuated airway inflammation.ConclusionThese results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.

Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model

“…Mice were sensitized intranasally with 25 μg HDM or vehicle on days 1, 8, and 15. Mice were challenged intranasally with 5 μg HDM on days 22, 23, and 24 [ 24 ]. Four hours after the final challenge, mice were euthanized by intraperitoneal injection with sodium pentobarbital.…”

“…BALF samples were collected as described previously [ 24 , 25 ]. Briefly, a 20-gauge tube was inserted into the trachea and the lungs were lavaged with 1 ml of saline twice.…”

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

“…BALF samples were collected as described previously [14]. Briefly, a 23-G tube was inserted into the trachea, followed by two lung lavages, each with 1 ml of saline.…”

“…After BAL, the right lung was isolated and homogenized in 50 mM Tris-buffered saline (pH 7.4) containing 1.0% Triton X-100, 0.1% sodium dodecyl sulfate, 150 mM sodium chloride, 0.5% sodium deoxycholate, 1 mM phenylmethylsulfonyl fluoride, 1 μg/ml aprotinin, 1 μg/ml leupeptin, and 1 mM Na 3 VO 4 . Lung homogenates were centrifuged at 10,000×g for 15 min, then supernatants were collected and stored at −80 °C until needed [14].…”

The Nonantibiotic Macrolide EM900 Attenuates House Dust Mite-Induced Airway Inflammation in a Mouse Model of Obesity-Associated Asthma

“…BALF samples were collected as described previously [24]. Briefly, a 23-G tube was inserted into the trachea, and lung lavage was performed twice, each with 1 mL of saline.…”