scholarly journals Inhibition of Both Cyclooxygenase-1 and -2 Promotes Epicutaneous Th2 and Th17 Sensitization and Allergic Airway Inflammation on Subsequent Airway Exposure to Protease Allergen in Mice

2021 ◽  
pp. 1-12
Author(s):  
Punyada Suchiva ◽  
Toshiro Takai ◽  
Seiji Kamijo ◽  
Natsuko Maruyama ◽  
Takehiko Yokomizo ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Cytokine Production ◽  
Allergic Airway Inflammation ◽  
Allergic Diseases ◽  
Specific Ige ◽  
House Dust Mites ◽  
Cyclooxygenase 1 ◽  
Cox Inhibitor ◽  
Allergen Sources ◽  
Th17 Cytokine

<b><i>Introduction:</i></b> Epicutaneous (e.c.) allergen exposure is an important route of sensitization toward allergic diseases in the atopic march. Allergen sources such as house dust mites contain proteases that involve in the pathogenesis of allergy. Prostanoids produced via pathways downstream of cyclooxygenases (COXs) regulate immune responses. Here, we demonstrate effects of COX inhibition with nonsteroidal anti-inflammatory drugs (NSAIDs) on e.c. sensitization to protease allergen and subsequent airway inflammation in mice. <b><i>Methods:</i></b> Mice were treated with NSAIDs during e.c. sensitization to a model protease allergen, papain, and/or subsequent intranasal challenge with low-dose papain. Serum antibodies, cytokine production in antigen-restimulated skin or bronchial draining lymph node (DLN) cells, and airway inflammation were analyzed. <b><i>Results:</i></b> In e.c. sensitization, treatment with a nonspecific COX inhibitor, indomethacin, promoted serum total and papain-specific IgE response and Th2 and Th17 cytokine production in skin DLN cells. After intranasal challenge, treatment with indomethacin promoted allergic airway inflammation and Th2 and Th17 cytokine production in bronchial DLN cells, which depended modestly or largely on COX inhibition during e.c. sensitization or intranasal challenge, respectively. Co-treatment with COX-1-selective and COX-2-selective inhibitors promoted the skin and bronchial DLN cell Th cytokine responses and airway inflammation more efficiently than treatment with either selective inhibitor. <b><i>Conclusion:</i></b> The results suggest that the overall effects of COX downstream prostanoids are suppressive for development and expansion of not only Th2 but also, unexpectedly, Th17 upon exposure to protease allergens via skin or airways and allergic airway inflammation.

scholarly journals IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite–induced asthma models

2017 ◽  
Vol 214 (10) ◽  
pp. 3037-3050 ◽  
Author(s):  
Takashi Ito ◽  
Koichi Hirose ◽  
Aiko Saku ◽  
Kenta Kono ◽  
Hiroaki Takatori ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
House Dust ◽  
House Dust Mite ◽  
Cytokine Production ◽  
Allergic Airway Inflammation ◽  
Lung Epithelial Cells ◽  
Intratracheal Administration ◽  
Lung Epithelial ◽  
Dust Mite

Previous studies have shown that IL-22, one of the Th17 cell–related cytokines, plays multiple roles in regulating allergic airway inflammation caused by antigen-specific Th2 cells; however, the underlying mechanism remains unclear. Here, we show that allergic airway inflammation and Th2 and Th17 cytokine production upon intratracheal administration of house dust mite (HDM) extract, a representative allergen, were exacerbated in IL-22-deficient mice. We also found that IL-22 induces Reg3γ production from lung epithelial cells through STAT3 activation and that neutralization of Reg3γ significantly exacerbates HDM-induced eosinophilic airway inflammation and Th2 cytokine induction. Moreover, exostatin-like 3 (EXTL3), a functional Reg3γ binding protein, is expressed in lung epithelial cells, and intratracheal administration of recombinant Reg3γ suppresses HDM-induced thymic stromal lymphopoietin and IL-33 expression and accumulation of type 2 innate lymphoid cells in the lung. Collectively, these results suggest that IL-22 induces Reg3γ production from lung epithelial cells and inhibits the development of HDM-induced allergic airway inflammation, possibly by inhibiting cytokine production from lung epithelial cells.

scholarly journals Diabetes Downregulates Allergen-Induced Airway Inflammation in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Vinicius F. Carvalho ◽  
Emiliano O. Barreto ◽  
Ana Carolina S. Arantes ◽  
Magda F. Serra ◽  
Tatiana Paula T. Ferreira ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Allergic Airway Inflammation ◽  
Allergic Diseases ◽  
Lavage Fluid ◽  
Airway Hyperreactivity ◽  
Eosinophil Infiltration ◽  
Mucus Production ◽  
Diabetes Induction

Previous studies described that allergic diseases, including asthma, occur less often than expected in patients with type 1 diabetes. Here, we investigated the influence of diabetes on allergic airway inflammation in a model of experimental asthma in mice. Diabetes was induced by intravenous injection of alloxan into 12 h-fasted A/J mice, followed by subcutaneous sensitization with ovalbumin (OVA) and aluminum hydroxide (Al(OH)3), on days 5 and 19 after diabetes induction. Animals were intranasally challenged with OVA (25 μg), from day 24 to day 26. Alloxan-induced diabetes significantly attenuated airway inflammation as attested by the lower number of total leukocytes in the bronchoalveolar lavage fluid, mainly neutrophils and eosinophils. Suppression of eosinophil infiltration in the peribronchiolar space and generation of eosinophilotactic mediators, such as CCL-11/eotaxin, CCL-3/MIP-1α, and IL-5, were noted in the lungs of diabetic sensitized mice. In parallel, reduction of airway hyperreactivity (AHR) to methacholine, mucus production, and serum IgE levels was also noted under diabetic conditions. Our findings show that alloxan diabetes caused attenuation of lung allergic inflammatory response in A/J mice, by a mechanism possibly associated with downregulation of IgE antibody production.

scholarly journals Changes in Pulmonary Function and Parasite Burden in Rats Infected with Strongyloides venezuelensis Concomitant with Induction of Allergic Airway Inflammation

2003 ◽  
Vol 71 (5) ◽  
pp. 2607-2614 ◽  
Author(s):  
Deborah Negrão-Corrêa ◽  
Micheline R. Silveira ◽  
Cynthia M. Borges ◽  
Danielle G. Souza ◽  
Mauro M. Teixeira
Keyword(s):  
Airway Inflammation ◽  
Mutual Influence ◽  
Pulmonary Inflammation ◽  
Allergic Airway Inflammation ◽  
Parasite Burden ◽  
Allergic Diseases ◽  
Lavage Fluid ◽  
Eosinophil Infiltration ◽  
Asthmatic Patients ◽  
Strongyloides Venezuelensis

ABSTRACT The prevalence of allergic diseases such as asthma has increased markedly over the past few decades. To evaluate the possible mutual influence of helminth infection and allergy, the combined effects of experimental allergic airway inflammation and infection with Strongyloides venezuelensis on various parasitological and inflammatory indices were evaluated in the rat. A challenge of immunized rats with aerosolized ovalbumin (OVA) resulted in eosinophilic inflammation that peaked 48 h after the challenge and was accompanied by airway hyperresponsiveness (AHR) to an intravenous acetylcholine challenge. S. venezuelensis infection concomitant with an OVA challenge of immunized rats resulted in prolonged pulmonary inflammation with increased eosinophil infiltration in bronchoalveolar lavage fluid but not in the lung tissue. These rats also showed a significant parasite burden reduction, especially during parasite migration through the lungs. However, the fecundity rates of worms that reached the intestine were similar in allergic and nonallergic animals. Despite airway inflammation, the increased responsiveness of the airways in the experimental asthma model was suppressed during parasite migration through the lungs (2 days). In contrast, parasite-induced AHR was unchanged 5 days after infection in immunized and challenged rats. In conclusion, infection with S. venezuelensis interfered with the onset of AHR following an antigen challenge of immunized rats. The ability of parasites to switch off functional airway responses is therapeutically relevant because we may learn from parasites how to modulate lung function and, hence, the AHR characteristic of asthmatic patients.

scholarly journals Allergen protease-induced Gsdmd p40 controls IL-33 secretion

2021 ◽  
Author(s):  
Bing Sun ◽  
Bin Wu ◽  
Dong Wu ◽  
Feng Shao ◽  
Yaguang Zhang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Critical Role ◽  
Allergic Airway Inflammation ◽  
Airway Epithelial Cells ◽  
Allergen Exposure ◽  
Lymphoid Cells ◽  
House Dust Mites ◽  
Airway Epithelial ◽  
Group 2 ◽  
Inflammatory Caspases

Abstract Interleukin (IL)-33, an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammation, such as that in asthma. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we demonstrated that Gasdermin D (Gsdmd) functions as a conduit for IL-33 secretion following allergen protease exposure. Gsdmd was rapidly cleaved into a functional neo-form, the N-terminal p40 fragment (p40 NT-Gsdmd), in the murine airway epithelium when cells were exposed to allergen proteases from fungi, house dust mites (HDMs), or bacteria. This cleavage event that produces the p40 Gsdmd fragment was independent of inflammatory caspases-1/11, as it could not be inhibited by caspase-1 and caspase-11 deficiency in murine cells. The functional p40 NT-Gsdmd fragment directly contributed to the secretion of both the nuclear full-length form and cytosolic mature form of IL-33. Both Gsdmd deficiency and blockade of the generation of p40 by amino acid mutation or deletion of residues 308–313 (ELRQQ) in the Gsdmd sequence could efficiently prevent IL-33 release in airway epithelial cells. In mice, Gsdmd deficiency prevented IL-33 release and hindered the activation of group 2 innate lymphoid cells (ILC2s), thus alleviating airway inflammation and lung tissue damage after stimulation with HDMs or papain. Our findings uncovered a mechanism of Gsdmd-mediated IL-33 release under allergen exposure and offer insight into Gsdmd cleavage prevention as a potential approach to reduce allergic airway inflammation.

scholarly journals Systemic and local cytokine profile and risk factors for persistent allergic airway inflammation in patients sensitised to house dust mite allergens

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura Tamasauskiene ◽  
Brigita Sitkauskiene
Keyword(s):  
Vitamin D ◽  
Airway Inflammation ◽  
House Dust ◽  
Allergic Airway Inflammation ◽  
Cytokine Profile ◽  
Nasal Lavage ◽  
House Dust Mites ◽  
Healthy Individuals ◽  
Ifn Gamma ◽  
Airway Diseases

Abstract Objective To evaluate cytokine profile, vitamin D status, symptom score and quality of life in patients with persistent allergic airway diseases sensitised to house dust mites (HDM) in comparison with healthy individuals. Material and methods Patients sensitized to HDM with persistent AR and having symptoms for at least 2 years with or without AA were involved into the study. Measurements of vitamin D level in serum and IL-10, IL-13, IL-17, IL-22, IL-33 and IFN-gamma in serum and nasal lavage were performed by ELISA. Results Eighty-one subjects were involved into the study. Serum IL-10 concentration was higher in patients with AR than in patients with AR and AA (6.71 ± 1.73 vs. 1.98 ± 0.24, p < 0.05). IFN-gamma level in nasal lavage was higher in patients with AR and AA than in patients with AR (p < 0.01) and healthy individuals (p < 0.05) (7.50 ± 0.37 vs. 6.80 ± 0.99 vs. 6.50 ± 0.22). Serum IL-22 negatively correlated with IL-22 in nasal lavage, whereas serum IFN-gamma positively correlated with IFN-gamma in nasal lavage. Positive correlation between serum IL-17 and total IgE and negative correlation between IL-17 in nasal lavage and eosinophils in nasal smear were found in patients with AR and AA. Serum IFN-gamma decreased the risk of AR for healthy individuals. Serum IL-10 and vitamin D decreased risk for development of AA for patients with AR. IL-22 in serum and IL-10 and IL-33 in nasal lavage increased this risk. Conclusion Novel cytokines such as IL-22, IL-17 and IL-33 and vitamin D may be involved in pathogenesis of persistent airway inflammation in patients sensitized to HDM.

HOUSE DUST MITE ALLERGENS: FROM NATIVE EXTRACTS TO MODIFIED PREPARATIONS

2021 ◽  
Author(s):  
Anna Vasilyeva ◽  
Valentina M. Berzhets ◽  
Nina S. Petrova ◽  
Svetlana V. Khlgatian ◽  
Stanislava Yu. Petrova ◽  
...  
Keyword(s):  
House Dust ◽  
Allergic Diseases ◽  
Specific Ige ◽  
Dermatophagoides Pteronyssinus ◽  
House Dust Mites ◽  
Dust Mites ◽  
Binding Reaction ◽  
Dust Mite ◽  
Allergenic Activity ◽  
Elisa Inhibition

The growth of allergic diseases dictates the need to develop new forms of therapeutic allergens with high immunogenic and low allergenic activity. For many years, our laboratory has been developing drugs for the diagnosis and treatment of house dust mites (HDM) allergies. The purpose of this study is to summarize the results of the five-year development of therapeutic preparations of HDM allergens. During this period, we obtained the following forms of therapeutic allergens: a granular sublingual dosage form of a mixed allergen from Dermatophagoides pteronyssinus (Der.p) and Dermatophagoides farinaе (Der.f) and a succinylated monomeric HDM allergoid Der.p. The physicochemical and immunobiological properties of the obtained preparations were studied by methods: electrophoresis in PAGE in the presence of SDS-sodium, micropoint immunoblot, ELISA, inhibition of the binding reaction of allergen-specific IgE in the sera of patients. The research results showed that the obtained preparations have a reduced allergenic and increased immunogenic activity in comparison with native extracts. The created forms of mite allergens can be further used to treat patients sensitized to HDM of the genus Dermatophagoides.

scholarly journals Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization

2016 ◽  
Vol 113 (18) ◽  
pp. 5059-5064 ◽  
Author(s):  
Charles B. Smarr ◽  
Woon Teck Yap ◽  
Tobias P. Neef ◽  
Ryan M. Pearson ◽  
Zoe N. Hunter ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Significant Risk ◽  
Allergic Airway Inflammation ◽  
Allergic Diseases ◽  
Soluble Antigen ◽  
Ag Nps ◽  
Th2 Responses ◽  
Allergy Treatment ◽  
Biodegradable Poly ◽  
Induction Of Tolerance

Specific immunotherapy (SIT) is the most widely used treatment for allergic diseases that directly targets the T helper 2 (Th2) bias underlying allergy. However, the most widespread clinical applications of SIT require a long period of dose escalation with soluble antigen (Ag) and carry a significant risk of adverse reactions, particularly in highly sensitized patients who stand to benefit most from a curative treatment. Thus, the development of safer, more efficient methods to induce Ag-specific immune tolerance is critical to advancing allergy treatment. We hypothesized that antigen-associated nanoparticles (Ag-NPs), which we have used to prevent and treat Th1/Th17-mediated autoimmune disease, would also be effective for the induction of tolerance in a murine model of Th2-mediated ovalbumin/alum-induced allergic airway inflammation. We demonstrate here that antigen-conjugated polystyrene (Ag-PS) NPs, although effective for the prophylactic induction of tolerance, induce anaphylaxis in presensitized mice. Antigen-conjugated NPs made of biodegradable poly(lactide-co-glycolide) (Ag-PLG) are similarly effective prophylactically, are well tolerated by sensitized animals, but only partially inhibit Th2 responses when administered therapeutically. PLG NPs containing encapsulated antigen [PLG(Ag)], however, were well tolerated and effectively inhibited Th2 responses and airway inflammation both prophylactically and therapeutically. Thus, we illustrate progression toward PLG(Ag) as a biodegradable Ag carrier platform for the safe and effective inhibition of allergic airway inflammation without the need for nonspecific immunosuppression in animals with established Th2 sensitization.

scholarly journals Intragastric and Intranasal Administration ofLactobacillus paracaseiNCC2461 Modulates Allergic Airway Inflammation in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Céline Pellaton ◽  
Sophie Nutten ◽  
Anne-Christine Thierry ◽  
Caroline Boudousquié ◽  
Nathalie Barbier ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Cell ◽  
T Regulatory Cells ◽  
Allergic Airway Inflammation ◽  
Probiotic Strain ◽  
Allergic Diseases ◽  
Cell Number ◽  
Intragastric Administration ◽  
Dependent Manner ◽  
Administration Routes

Introduction. Preclinical and clinical evidences for a role of oral probiotics in the management of allergic diseases are emerging.Aim. We aimed at testing the immunomodulatory effects of intranasalversusintragastric administration ofLactobacillus paracaseiNCC2461 in a mouse model of allergic airway inflammation and the specificity of different probiotics by comparingL. paracaseiNCC2461 toLactobacillus plantarumNCC1107.Methods.L. paracaseiNCC2461 orL. plantarumNCC1107 strains were administered either intragastrically (NCC2461) or intranasally (NCC2461 or NCC1107) to OVA-sensitized mice challenged with OVA aerosols. Inflammatory cell recruitment into BALF, eotaxin and IL-5 production in the lungs were measured.Results. IntranasalL. paracaseiNCC2461 efficiently protected sensitized mice upon exposure to OVA aerosols in a dose-dependent manner as compared to control mice. Inflammatory cell number, eotaxin and IL-5 were significantly reduced in BALF. Intranasal supplementation ofL. paracaseiNCC2461 was more potent than intragastric application in limiting the allergic response and possibly linked to an increase in T regulatory cells in the lungs. Finally, intranasalL. plantarumNCC1107 reduced total and eosinophilic lung inflammation, but increased neutrophilia and macrophages infiltration.Conclusion. A concerted selection of intervention schedule, doses, and administration routes (intranasal versus intragastric) may markedly contribute to modulate airway inflammation in a probiotic strain-specific manner.

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