scholarly journals Effect of Ozone on Allergic Airway Inflammation

2022 ◽  
Author(s):  
Mehrdad Arjomandi ◽  
Hofer Wong ◽  
Rachel Tenney ◽  
Nina Holland ◽  
John R Balmes
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Responses ◽  
Intermittent Exercise ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Gstm1 Null Genotype ◽  
Markers Of Inflammation ◽  
Cytokine Responses ◽  
Increased Risk ◽  
Background Exposure

Background: Exposure to O3 has been associated with increased risk of exacerbations of asthma, but the underlying mechanisms are not well studied. We hypothesized that O3 exposure would enhance airway inflammatory responses to allergen and the GSTM1 null genotype would modulate this enhancement. Procedures: In a cross-over design, 10 asthmatic subjects (50% with GSTM1 null genotype) who had specific sensitization to Dermatophagoides pteronyssinus (DP) were exposed to 160 ppb O3 or filtered air (FA) control for 4 h with intermittent exercise on two separate days at least three weeks apart. 20 h post-exposure, endobronchial challenge with DP allergen, and sham normal saline (NS) instillation, were performed in two separate lung lobes. Six h later, a second bronchoscopy was performed to collect bronchoalveolar lavage (BAL) fluid from the DP- and NS-challenged lobes for analyses of cellular and biochemical markers of inflammation. Multiple variable regression was used to compare cell and cytokine responses across the four exposure groups (FA-NS, O3-NS, FA-DP, O3-DP). Effect modification by GSTM1 genotype was assessed in stratified regressions. Main Findings: BAL eosinophil and lymphocyte counts were increased in segments challenged with DP compared to segments that received sham challenges (p<0.01). DP challenge compared to sham challenge also caused a significant increase in BAL concentrations of the Th2 cytokines IL-4, IL-5, IL-10, and IL-13 (p<0.03 for all comparisons). O3 exposure did not significantly affect BAL cells or cytokine levels although BAL neutrophil count with DP challenge was non-significantly higher after O3 compared to after FA exposure (p<0.11). Compared to GSTM1-present subjects, GSTM1-null subjects had significantly reduced inflammatory responses including lower eosinophil (p<0.041) and IL-4 (p<0.014) responses to DP challenge after O3 exposure. Conclusions: O3 appears to have mixed effects on allergen-induced airway inflammation. While O3 did not cause a clear differential effect on airway cellular or cytokine responses to allergen challenge, those responses did appear to be modulated by the antioxidant enzyme, GSTM1, as evident by the attenuation of airway inflammatory responses to allergen after O3 exposure in the absence of the gene.

Exhaled nitric oxide estimation by a simple and efficient noninvasive technique and its utility as a marker of airway inflammation in mice

2009 ◽  
Vol 107 (1) ◽  
pp. 295-301 ◽  
Author(s):  
Tanveer Ahmad ◽  
Ulaganathan Mabalirajan ◽  
Duraisamy Arul Joseph ◽  
Lokesh Makhija ◽  
Vijay Pal Singh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Airway Inflammation ◽  
Airway Remodeling ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Ambient Air ◽  
Exhaled Nitric Oxide ◽  
Noninvasive Technique ◽  
Modified Method ◽  
Chronic Models

Allergic airway inflammation (AI) is commonly associated with enhanced exhaled nitric oxide (ENO) in both humans and mice. Since mouse models are being used to understand various mechanisms of asthma, a noninvasive, simple, and reproducible method to determine ENO in mice is required for serial nonterminal assessment that can be used independent of environmental situations in which the ambient air contains substantial amounts of NO as a contaminant. The aim of this study was to noninvasively measure ENO in individual mice and to test its utility as a marker of AI in different models of allergic AI. We modified the existing ENO measuring methods by incorporating flushing and washout steps that allowed simple but reliable measurements under highly variable ambient NO conditions (1–100 ppb). This method was used to serially follow ENO in acute and chronic models of allergic AI in mice. ENO was reproducibly measured by this modified method and was positively correlated to AI in both acute and chronic models of asthma but was not independently related to airway remodeling. Resolution of AI and other related parameters in dexamethasone-treated mice resulted in reduction of ENO, further confirming this association. Restriction of allergen challenge to pulmonary but not nasal airways was associated with a smaller increase in ENO compared with allergen challenge to both. Hence, ENO can now be reliably measured in mice independent of ambient NO levels and is a valid biomarker for AI. However, nasal and pulmonary airways are likely to be independent sources of ENO, and any results must be interpreted as such.

scholarly journals 2215

2017 ◽  
Vol 1 (S1) ◽  
pp. 3-3
Author(s):  
Timothy P. Moran ◽  
Robert M. Immormino ◽  
Hideki Nakano ◽  
David Peden ◽  
Donald N. Cook
Keyword(s):  
Flow Cytometry ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Allergic Airway Inflammation ◽  
Surface Protein ◽  
Fold Increase ◽  
Deficient Mice

OBJECTIVES/SPECIFIC AIMS: Allergic asthma is a chronic lung disease driven by inappropriate inflammatory responses against inhaled allergens. Neuropilin-2 (NRP2) is a pleiotropic transmembrane receptor expressed in the lung, but its role in allergic airway inflammation is unknown. Here, we characterized NRP2 expression in lung immune cells and investigated the effects of NRP2 deficiency on airway inflammation. METHODS/STUDY POPULATION: NRP2 expression by lung immune cells from NRP2 reporter mice was determined by flow cytometry. NRP2 expression by human alveolar macrophages (AM) from healthy individuals was determined by mRNA analysis and flow cytometry. Airway inflammation in NRP2-deficient mice was assessed by bronchoalveolar lavage (BAL) cytology and inflammatory gene expression in lung tissue. RESULTS/ANTICIPATED RESULTS: NRP2 expression in lung immune cells was negligible under steady-state conditions. In contrast, inhalational exposure to lipopolysaccharide (LPS) adjuvant dramatically induced NRP2 expression in AM, as 63.3% of AM from LPS-treated mice were NRP2+ compared with 1.5% of AM from control mice. Ex vivo treatment of human AM with LPS resulted in a 1.5-fold and 2.6-fold increase in NRP2 mRNA and surface protein expression, respectively. Compared to littermate controls, NRP2-deficient mice had greater numbers of BAL leukocytes and increased lung expression of the T helper type 2 cytokines IL-4 and IL-5. Furthermore, NRP2 deficiency resulted in stochastic development of allergic airway inflammation, as spontaneous airway eosinophilia was detected in 25% (2/8) of NRP2-deficient mice compared with 0% (0/8) of littermate controls. DISCUSSION/SIGNIFICANCE OF IMPACT: NRP2 is expressed by activated human and murine AM and suppresses the spontaneous development of allergic airway inflammation. These findings suggest that NRP2 may play a key role in allergic asthma pathogenesis, and could prove to be an important therapeutic target in patients with asthma and other allergic diseases.

scholarly journals Androgen signaling negatively controls group 2 innate lymphoid cells

2017 ◽  
Vol 214 (6) ◽  
pp. 1581-1592 ◽  
Author(s):  
Sophie Laffont ◽  
Eve Blanquart ◽  
Magali Savignac ◽  
Claire Cénac ◽  
Gilles Laverny ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Allergic Airway Inflammation ◽  
Innate Lymphoid Cells ◽  
Protective Role ◽  
Lymphoid Cells ◽  
Peripheral Tissues ◽  
Group 2

Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33–driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33–mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33–driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.

scholarly journals Role of the phosphoinositide 3-kinase p110δ in generation of type 2 cytokine responses and allergic airway inflammation

2007 ◽  
Vol 37 (2) ◽  
pp. 416-424 ◽  
Author(s):  
Baher F. Nashed ◽  
Tingting Zhang ◽  
Monther Al-Alwan ◽  
Ganesh Srinivasan ◽  
Andrew J. Halayko ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Cytokine Responses ◽  
Phosphoinositide 3 Kinase

scholarly journals Specific Immunotherapy in a Murine Model of Grass Pollen (Phl p5b)-Induced Airway Inflammation

2021 ◽  
Vol 2 ◽  
Author(s):  
Matthias Stiehm ◽  
Marcus Peters
Keyword(s):  
Airway Inflammation ◽  
Murine Model ◽  
Grass Pollen ◽  
Specific Immunotherapy ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Interleukin 5 ◽  
Grass Pollen Allergen ◽  
Adjuvant Effects

Background: The use of ovalbumin as a model allergen in murine models of allergic asthma is controversially discussed since it is not an aeroallergen and sensitization can only be achieved by using strong Th2-inducing adjuvants. Therefore, in this study, a murine model of asthma has been established in which sensitization against the major grass pollen allergen Phl p5b was performed without using aluminum hydroxide (alum). We used this model for specific immunotherapy.Methods: Female, 5–6-week-old mice were sensitized by six subcutaneous (s.c.) injections of 20 μg Phl p5b followed by four provocations to induce allergic airway inflammation. For desensitization, 1 mg of Phl p5b was injected subcutaneously during allergen challenge for one to a maximum of four times. Three days after the last challenge, the allergic immune response was analyzed.Results: Sensitized and challenged animals showed a significant infiltration of eosinophils into the airways, and the production of interleukin-5 (IL-5) by in vitro re-stimulated splenocytes could be detected. Furthermore, hyper-responsiveness of the airways was verified by invasive measurement of airway resistance in methacholine-challenged animals. Desensitized animals showed a significant reduction of all parameters.Conclusion: In this study, a murine model of asthma has successfully been established by sensitization against the clinically relevant allergen Phl p5b without using alum. S.c. injection of allergen dose dependently led to desensitization of sensitized mice. We suggest that this model is useful to study adjuvant effects of immune modulatory substances on immunotherapy without the interference of alum.

scholarly journals Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung.

1995 ◽  
Vol 181 (3) ◽  
pp. 1211-1216 ◽  
Author(s):  
M E Rothenberg ◽  
A D Luster ◽  
C M Lilly ◽  
J M Drazen ◽  
P Leder
Keyword(s):  
Amino Acids ◽  
Guinea Pig ◽  
Mrna Expression ◽  
Airway Inflammation ◽  
Late Phase ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Human Macrophage ◽  
Mrna Levels ◽  
Coding Region

Eotaxin is a member of the C-C family of chemokines and is related during antigen challenge in a guinea pig model of allergic airway inflammation (asthma). Consistent with its putative role in eosinophilic inflammation, eotaxin induces the selective infiltration of eosinophils when injected into the lung and skin. Using a guinea pig lung cDNA library, we have cloned full-length eotaxin cDNA. The cDNA encodes a protein of 96 amino acids, including a putative 23-amino acid hydrophobic leader sequence, followed by 73 amino acids composing the mature active eotaxin protein. The protein-coding region of this cDNA is 73, 71, 50, and 48% identical in nucleic acid sequence to those of human macrophage chemoattractant protein (MCP) 3, MCP-1, macrophage inflammatory protein (MIP) 1 alpha, and RANTES, respectively. Analysis of genomic DNA suggested that there is a single eotaxin gene in guinea pig which is apparently conserved in mice. High constitutive levels of eotaxin mRNA expression were observed in the lung, while the intestines, stomach, spleen, liver, heart, thymus, testes, and kidney expressed lower levels. To determine if eotaxin mRNA levels are elevated during allergen-induced eosinophilic airway inflammation, ovalbumin (OVA)-sensitized guinea pigs were challenged with aerosolized antigen. Compared with the lungs from saline-challenged animals, eotaxin mRNA levels increased sixfold within 3 h and returned to baseline by 6 h. Thus, eotaxin mRNA levels are increased in response to allergen challenge during the late phase response. The identification of constitutive eotaxin mRNA expression in multiple tissues suggests that in addition to regulating airway eosinophilia, eotaxin is likely to be involved in eosinophil recruitment into other tissues as well as in baseline tissue homing.

MTOR suppresses autophagy-mediated production of IL25 in allergic airway inflammation

Thorax ◽  
2020 ◽  
Vol 75 (12) ◽  
pp. 1047-1057
Author(s):  
Wen Li ◽  
Yinfang Wu ◽  
Yun Zhao ◽  
Zhouyang Li ◽  
Haixia Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Bronchial Epithelium ◽  
Airway Epithelial Cells ◽  
House Dust Mites ◽  
Airway Epithelial ◽  
Asthmatic Patients

IntroductionAirway epithelial cells are recognised as an essential controller for the initiation and perpetuation of asthmatic inflammation, yet the detailed mechanisms remain largely unknown. This study aims to investigate the roles and mechanisms of the mechanistic target of rapamycin (MTOR)–autophagy axis in airway epithelial injury in asthma.MethodsWe examined the MTOR–autophagy signalling in airway epithelium from asthmatic patients or allergic mice induced by ovalbumin or house dust mites, or in human bronchial epithelial (HBE) cells. Furthermore, mice with specific MTOR knockdown in airway epithelium and autophagy-related lc3b-/- mice were used for allergic models.ResultsMTOR activity was decreased, while autophagy was elevated, in airway epithelium from asthmatic patients or allergic mice, or in HBE cells treated with IL33 or IL13. These changes were associated with upstream tuberous sclerosis protein 2 signalling. Specific MTOR knockdown in mouse bronchial epithelium augmented, while LC3B deletion diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by MTOR deficiency was also ameliorated in lc3b-/- mice. Mechanistically, autophagy was induced later than the emergence of allergen-initiated inflammation, particularly IL33 expression. MTOR deficiency increased, while knocking out of LC3B abolished the production of IL25 and the eventual airway inflammation on allergen challenge. Blocking IL25 markedly attenuated the exacerbated airway inflammation in MTOR-deficiency mice.ConclusionCollectively, these results demonstrate that allergen-initiated inflammation suppresses MTOR and induces autophagy in airway epithelial cells, which results in the production of certain proallergic cytokines such as IL25, further promoting the type 2 response and eventually perpetuating airway inflammation in asthma.

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