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Molecular Medicine in Asthma and Allergic Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 27546

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Special Issue Editors

Dr. Blanca Cárdaba

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Guest Editor

Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), 28040 Madrid, Spain
Interests: asthma; system biology; allergic biomarkers
Special Issues, Collections and Topics in MDPI journals

Dr. Jose Antonio Cañas Mañas

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Guest Editor

Allergy Research Group, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
Interests: asthma; allergy; eosinophils; microRNAs; food allergy; dendritic cells; regulatory T cells; basophils; flow cytometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Allergic diseases and asthma are common, complex, heterogeneous diseases with a wide spectrum of clinical symptoms, essentially due to their multifactorial nature. However, despite the multiple advances on allergen characterization and molecular and cellular bases that underlie these diseases, there are many essential aspects that should be improved at different levels. For example, with the exception of allergen-specific immunotherapy (SIT) in the case of diagnosis with known allergens, most treatments are indicated to control the disease and not to cure it; sometimes, the diagnosis and the specific treatments, e.g., for polyallergic patients, is not easy; additionally, there are no clear biomarkers to predict or prevent what patients will develop the most severe clinical forms of a disease, etc.

Advances in molecular and cellular biology and genetic engineering, driven by new techniques of massive studies at the genomic, proteomic, transcriptomic, epigenomic, metabolomic, etc. levels aided by complex computer analysis systems are allowing the study of this type of diseases to be approached from other perspectives, providing new key tools that could drive new molecular medicine in the future.

In this Special Issue, we invite original articles or reviews that address allergic diseases and asthma, preferably from a molecular perspective, providing new knowledge on diagnostic, prevention, or novelty treatments supported by future molecular medicine applicable to these complex diseases.

Dr. Blanca Cárdaba
Dr. Jose Antonio Cañas Mañas
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

allergy
asthma
biologic treatments
molecular biomarkers
molecular diagnosis
endotypes
immunomodulation
vaccines

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Related Special Issue

Molecular Medicine in Asthma and Allergic Diseases 2.0 in International Journal of Molecular Sciences (2 articles)

Published Papers (9 papers)

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Editorial

Jump to: Research, Review

3 pages, 415 KiB

Open AccessEditorial

From the Allergic Cascade to the Epithelium-Driven Disease: The Long Road of Bronchial Asthma

by Christian Domingo and Rosa M. Mirapeix

Int. J. Mol. Sci. 2023, 24(3), 2716; https://doi.org/10.3390/ijms24032716 - 1 Feb 2023

Cited by 4 | Viewed by 1666

Abstract

In medicine, much of the progress made is due to the emergence of new drugs [...] Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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Research

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16 pages, 3601 KiB

Open AccessArticle

IL-22 Is Deleterious along with IL-17 in Allergic Asthma but Is Not Detrimental in the Comorbidity Asthma and Acute Pneumonia

by Amanda Goulart, Mèdéton Mahoussi Michaël Boko, Nubia Sabrina Martins, Ana Flávia Gembre, Rômulo Silva de Oliveira, Sandra Patrícia Palma-Albornoz, Thais Bertolini, Paulo Eduardo Martins Ribolla, Leandra Naira Zambelli Ramalho, Thais Fernanda de Campos Fraga-Silva and Vânia Luiza Deperon Bonato

Int. J. Mol. Sci. 2023, 24(13), 10418; https://doi.org/10.3390/ijms241310418 - 21 Jun 2023

Cited by 1 | Viewed by 1873

Abstract

There is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. To investigate the role of IL-22, we used IL-22 deficient mice (IL-22 KO) sensitized and challenged with ovalbumin (OVA) and compared with wild type (WT) animals exposed to OVA. IL-22 KO animals exposed to OVA showed a decreased number and frequency of eosinophils, IL-5 and IL-13 in the airways, reduced mucus production and pulmonary inflammation. In addition, IL-22 KO animals exhibited a decreased percentage and number of lung CD11c⁺CD11b⁺ cells and increased apoptosis of eosinophils. Th17 cell transfer generated from IL-22 KO to animals previously sensitized and challenged with OVA caused a reduction in eosinophil frequency and number in the airways compared to animals transferred with Th17 cells generated from WT mice. Therefore, IL-22 is deleterious with concomitant secretion of IL-17. Our findings show a pro-inflammatory role for IL-22, confirmed in a model of allergen-free and allergen-specific immunotherapy. Moreover, during the comorbidity asthma and pneumonia that induces neutrophil inflammation, IL-22 was not detrimental. Our results show that targeting IL-22 would negatively affect the survival of eosinophils, reduce the expansion or migration of CD11c⁺CD11b⁺ cells, and negatively regulate allergic asthma. Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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15 pages, 4760 KiB

Open AccessArticle

Sophoraflavanone G from Sophora flavescens Ameliorates Allergic Airway Inflammation by Suppressing Th2 Response and Oxidative Stress in a Murine Asthma Model

by Meng-Chun Wang, Wen-Chung Huang, Li-Chen Chen, Kuo-Wei Yeh, Chwan-Fwu Lin and Chian-Jiun Liou

Int. J. Mol. Sci. 2022, 23(11), 6104; https://doi.org/10.3390/ijms23116104 - 29 May 2022

Cited by 14 | Viewed by 3037

Abstract

Sophoraflavanone G (SG), isolated from Sophora flavescens, has anti-inflammatory and anti-tumor bioactive properties. We previously showed that SG promotes apoptosis in human breast cancer cells and leukemia cells and reduces the inflammatory response in lipopolysaccharide-stimulated macrophages. We investigated whether SG attenuates airway hyper-responsiveness (AHR) and airway inflammation in asthmatic mice. We also assessed its effects on the anti-inflammatory response in human tracheal epithelial cells. Female BALB/c mice were sensitized with ovalbumin, and asthmatic mice were treated with SG by intraperitoneal injection. We also exposed human bronchial epithelial BEAS-2B cells to different concentrations of SG to evaluate its effects on inflammatory cytokine levels. SG treatment significantly reduced AHR, eosinophil infiltration, goblet cell hyperplasia, and airway inflammation in the lungs of asthmatic mice. In the lungs of ovalbumin-sensitized mice, SG significantly promoted superoxide dismutase and glutathione expression and attenuated malondialdehyde levels. SG also suppressed levels of Th2 cytokines and chemokines in lung and bronchoalveolar lavage samples. In addition, we confirmed that SG decreased pro-inflammatory cytokine, chemokine, and eotaxin expression in inflammatory BEAS-2B cells. Taken together, our data demonstrate that SG shows potential as an immunomodulator that can improve asthma symptoms by decreasing airway-inflammation-related oxidative stress. Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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16 pages, 1765 KiB

Open AccessArticle

Identification of Epitopes on Rhinovirus 89 Capsid Proteins Capable of Inducing Neutralizing Antibodies

by Katarzyna Niespodziana, Clarissa R. Cabauatan, Petra Pazderova, Phyllis C. Vacal, Judith Wortmann, Walter Keller, Peter Errhalt and Rudolf Valenta

Int. J. Mol. Sci. 2022, 23(9), 5113; https://doi.org/10.3390/ijms23095113 - 4 May 2022

Cited by 2 | Viewed by 2400

Abstract

Rhinoviruses (RVs) are major causes of the common cold, but they can also trigger exacerbations of asthma. More than 160 different RV strains exist and can be classified into three genetic species (RV-A, RV-B and RV-C) which bind to different receptors on human cells including intracellular adhesion molecule 1 (ICAM-1), the low-density lipoprotein receptor (LDLR) or the cadherin-related family member 3 (CDHR3). Epitopes located in the RV capsid have mainly been determined for RV2, a minor-group RV-A strain binding to LDLR, and for RV14, a major-group RV-B strain binding to ICAM-1. In order to study epitopes involved in the neutralization of RV89, an ICAM-1-binding RV-A strain which is highly different from RV2 and RV14 in terms of receptor specificity and sequence, respectively, we analyzed the specificity and epitopes of a highly neutralizing antiserum using recombinantly produced RV89 capsid proteins (VP1, VP2, VP3 and VP4), recombinant fragments and synthetic overlapping peptides thereof. We found that the antiserum which neutralized in vitro RV89 infection up to a dilution of 1:24,000 reacted with the capsid proteins VP1 and VP2 but not with VP3 and VP4. The neutralizing antibodies recognized recombinant fragments comprising approximately 100 amino acids of the N- and C-terminus of VP1 and the middle part of VP2, in particular, three peptides which, according to molecular modeling based on the three-dimensional structure of RV16, were surface-exposed on the viral capsid. Two recombinant fusion proteins containing the identified peptides fused to hepatitis B (HBV)-derived preS as a carrier protein induced upon immunization of rabbits antibodies capable of neutralizing in vitro RV89 infections. Interestingly, the virus-neutralizing epitopes determined for RV89 corresponded to those determined for minor-group RV2 binding to LDL and major-group RV14 belonging to the RV-B species, which are highly different from RV89. Our results indicate that highly different RV strains, even when reacting with different receptors, seem to engage similar parts of their capsid in the infection process. These results may be important for the design of active and passive immunization strategies for RV. Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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13 pages, 2684 KiB

Open AccessArticle

Storage Mite Precision Allergy Molecular Diagnosis in the Moderate-to-Severe T2-High Asthma Phenotype

by Ruperto González-Pérez, Paloma Poza-Guedes, Fernando Pineda, Miriam Castillo and Inmaculada Sánchez-Machín

Int. J. Mol. Sci. 2022, 23(8), 4297; https://doi.org/10.3390/ijms23084297 - 13 Apr 2022

Cited by 8 | Viewed by 2427

Abstract

Storage mites (SM) may induce allergic respiratory symptoms in sensitized individuals, in both rural and urban settings. The relationship among specific IgE reactions to determined groups of SM allergens in the coincident asthma pheno-endotypes has not yet been investigated. We aimed to study a Precision Allergy Molecular Diagnosis (PAMD@) model to depict the SM molecular profile in individuals presenting with Type-2 inflammation, in two different (moderate and severe) asthma phenotypes. A customized PAMD@ panel, including SM allergens and their concurrent protein allergenic characterization was investigated. Mite group 2 allergens were most frequently recognized, including Lep d 2 (83.45%), followed by Gly d 2 (69.17%) and Tyr p 2 (47,37%), in 133/164 asthmatic subjects. Blo t 5 and Blo t 21 exhibited significant higher titres in both asthma groups. Although relevant mite group 2 allergens cross-reactivity is suggested, individualized sensitization patterns were relevantly identified. The present PAMD@ panel confirmed the dominance of mite group 2 allergens in moderate-to-severe T2 asthmatics. A broadly heterogeneous molecular repertoire of SM allergens was found in all subjects, regardless of their asthma severity. Blomia tropicalis deserves special attention in certain territories, as diagnostic and/or therapeutic approaches merely based on Pyroglyphidae mites may be insufficient. Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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28 pages, 3222 KiB

Open AccessArticle

Asthmatic Eosinophils Alter the Gene Expression of Extracellular Matrix Proteins in Airway Smooth Muscle Cells and Pulmonary Fibroblasts

by Ieva Janulaityte, Andrius Januskevicius, Airidas Rimkunas, Jolita Palacionyte, Astra Vitkauskiene and Kestutis Malakauskas

Int. J. Mol. Sci. 2022, 23(8), 4086; https://doi.org/10.3390/ijms23084086 - 7 Apr 2022

Cited by 13 | Viewed by 2872

Abstract

The impaired production of extracellular matrix (ECM) proteins by airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) is a part of airway remodeling in asthma. This process might be influenced by eosinophils that migrate to the airway and abundantly secrete various cytokines, including TGF-β. We aimed to investigate the effect of asthmatic eosinophils on the gene expression of ECM proteins in ASMC and PF. A total of 34 study subjects were recruited: 14 with allergic asthma (AA), 9 with severe non-allergic eosinophilic asthma (SNEA), and 11 healthy subjects (HS). All AA patients underwent bronchial allergen challenge with D. pteronyssinus. The peripheral blood eosinophils were isolated using high-density centrifugation and magnetic separation. The individual cell cultures were made using hTERT ASMC and MRC-5 cell lines and the subjects’ eosinophils. The gene expression of ECM and the TGF-β signaling pathway was analyzed using qRT-PCR. We found that asthmatic eosinophils significantly promoted collagen I, fibronectin, versican, tenascin C, decorin, vitronectin, periostin, vimentin, MMP-9, ADAM33, TIMP-1, and TIMP-2 gene expression in ASMC and collagen I, collagen III, fibronectin, elastin, decorin, MMP-2, and TIMP-2 gene expression in PF compared with the HS eosinophil effect. The asthmatic eosinophils significantly increased the gene expression of several canonical and non-canonical TGF-β signaling pathway components in ASMC and PF compared with the HS eosinophil effect. The allergen-activated AA and SNEA eosinophils had a greater effect on these changes. In conclusion, asthmatic eosinophils, especially SNEA and allergen-activated eosinophils, imbalanced the gene expression of ECM proteins and their degradation-regulating proteins. These changes were associated with increased gene expression of TGF-β signaling pathway molecules in ASMC and PF. Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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Review

Jump to: Editorial, Research

15 pages, 319 KiB

Open AccessReview

Melatonin in Dermatologic Allergic Diseases and Other Skin Conditions: Current Trends and Reports

by Iva Bešlić, Liborija Lugović-Mihić, Alen Vrtarić, Ante Bešlić, Ivana Škrinjar, Milena Hanžek, Danijel Crnković and Marinko Artuković

Int. J. Mol. Sci. 2023, 24(4), 4039; https://doi.org/10.3390/ijms24044039 - 17 Feb 2023

Cited by 12 | Viewed by 5564

Abstract

Melatonin is the main hormone that regulates the sleep cycle, and it is mostly produced by the pineal gland from the amino acid tryptophan. It has cytoprotective, immunomodulatory, and anti-apoptotic effects. Melatonin is also one of the most powerful natural antioxidants, directly acting on free radicals and the intracellular antioxidant enzyme system. Furthermore, it participates in antitumor activity, hypopigmentation processes in hyperpigmentary disorders, anti-inflammatory, and immunomodulating activity in inflammatory dermatoses, maintaining the integrity of the epidermal barrier and thermoregulation of the body. Due predominantly to its positive influence on sleep, melatonin can be used in the treatment of sleep disturbances for those with chronic allergic diseases accompanied by intensive itching (such as atopic dermatitis and chronic spontaneous urticaria). According to the literature data, there are also many proven uses for melatonin in photoprotection and skin aging (due to melatonin’s antioxidant effects and role in preventing damage due to DNA repair mechanisms), hyperpigmentary disorders (e.g., melasma) and scalp diseases (such as androgenic alopecia and telogen effluvium). Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

12 pages, 1040 KiB

Open AccessReview

The Utility of Nasal Challenges to Phenotype Asthma Patients

by Guillermo Bentabol-Ramos, Rocio Saenz de Santa Maria-Garcia, Monica Vidal-Diaz, Ibon Eguiluz-Gracia and Almudena Testera-Montes

Int. J. Mol. Sci. 2022, 23(9), 4838; https://doi.org/10.3390/ijms23094838 - 27 Apr 2022

Cited by 3 | Viewed by 2499

Abstract

Asthma is a heterogeneous disease in terms of both phenotype and response to therapy. Therefore, there is a great need for clinically applicable tools allowing for improved patient classification, and selection for specific management approaches. Some interventions are highly helpful in selected patients (e.g., allergen immunotherapy or aspirin desensitization), but they are costly and/or difficult to implement. Currently available biomarkers measurable in peripheral blood or exhaled air display many limitations for asthma phenotyping and cannot identify properly the specific triggers of the disease (e.g., aeroallergens or NSAID). The united airway concept illustrates the relevant epidemiological and pathophysiological links between the upper and lower airways. This concept has been largely applied to patient management and treatment, but its diagnostic implications have been less often explored. Of note, a recent document by the European Academy of Allergy and Clinical Immunology proposes the use of nasal allergen challenge to confirm the diagnosis of allergic asthma. Similarly, the nasal challenge with lysine acetylsalicylate (L-ASA) can be used to identify aspirin-sensitive asthma patients. In this review, we will summarize the main features of allergic asthma and aspirin-exacerbated respiratory disease and will discuss the methodology of nasal allergen and L-ASA challenges with a focus on their capacity to phenotype the inflammatory disease affecting both the upper and lower airways. Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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21 pages, 683 KiB

Open AccessReview

Asthma and Allergy: Unravelling a Tangled Relationship with a Focus on New Biomarkers and Treatment

by Pablo Rodriguez del Rio, Andrew H. Liu, Magnus P. Borres, Eva Södergren, Fabio Iachetti and Thomas B. Casale

Int. J. Mol. Sci. 2022, 23(7), 3881; https://doi.org/10.3390/ijms23073881 - 31 Mar 2022

Cited by 13 | Viewed by 3624

Abstract

Asthma is a major driver of health care costs across ages. Despite widely disseminated asthma-treatment guidelines and a growing variety of effective therapeutic options, most patients still experience symptoms and/or refractoriness to standard of care treatments. As a result, most patients undergo a further intensification of therapy to optimize symptom control with a subsequent increased risk of side effects. Raising awareness about the relevance of evaluating aeroallergen sensitizations in asthmatic patients is a key step in better informing clinical practice while new molecular tools, such as the component resolved diagnosis, may be of help in refining the relationship between sensitization and therapeutic recommendations. In addition, patient care should benefit from reliable, easy-to-measure and clinically accessible biomarkers that are able to predict outcome and disease monitoring. To attain a personalized asthma management and to guide adequate treatment decisions, it is of paramount importance to expand clinicians’ knowledge about the tangled relationship between asthma and allergy from a molecular perspective. Our review explores the relevance of allergen testing along the asthma patient’s journey, with a special focus on recurrent wheezing children. Here, we also discuss the unresolved issues regarding currently available biomarkers and summarize the evidence supporting the eosinophil-derived neurotoxin as promising biomarker. Full article

(This article belongs to the Special Issue Molecular Medicine in Asthma and Allergic Diseases)

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