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Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs

Biological sex influences disease severity, prevalence and response to therapy in allergic asthma. However, allergen-mediated sex-specific changes in lung protein biomarkers remain undefined. Here, we report sex-related differences in specific proteins secreted in the lungs of both mice and humans,...

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Autores principales: Hemshekhar, Mahadevappa, Mostafa, Dina H. D., Spicer, Victor, Piyadasa, Hadeesha, Maestre-Batlle, Danay, Bolling, Anette K., Halayko, Andrew J., Carlsten, Christopher, Mookherjee, Neeloffer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273854/
https://www.ncbi.nlm.nih.gov/pubmed/35837410
http://dx.doi.org/10.3389/fimmu.2022.923986
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author Hemshekhar, Mahadevappa
Mostafa, Dina H. D.
Spicer, Victor
Piyadasa, Hadeesha
Maestre-Batlle, Danay
Bolling, Anette K.
Halayko, Andrew J.
Carlsten, Christopher
Mookherjee, Neeloffer
author_facet Hemshekhar, Mahadevappa
Mostafa, Dina H. D.
Spicer, Victor
Piyadasa, Hadeesha
Maestre-Batlle, Danay
Bolling, Anette K.
Halayko, Andrew J.
Carlsten, Christopher
Mookherjee, Neeloffer
author_sort Hemshekhar, Mahadevappa
collection PubMed
description Biological sex influences disease severity, prevalence and response to therapy in allergic asthma. However, allergen-mediated sex-specific changes in lung protein biomarkers remain undefined. Here, we report sex-related differences in specific proteins secreted in the lungs of both mice and humans, in response to inhaled allergens. Female and male BALB/c mice (7-8 weeks) were intranasally challenged with the allergen house dust mite (HDM) for 2 weeks. Bronchoalveolar lavage fluid (BALF) was collected 24 hour after the last HDM challenge from allergen-naïve and HDM-challenged mice (N=10 per group, each sex). In a human study, adult participants were exposed to nebulized (2 min) allergens (based on individual sensitivity), BALF was obtained after 24 hour (N=5 each female and male). The BALF samples were examined in immunoblots for the abundance of 10 proteins shown to increase in response to allergen in both murine and human BALF, selected from proteomics studies. We showed significant sex-bias in allergen-driven increase in five out of the 10 selected proteins. Of these, increase in eosinophil peroxidase (EPX) was significantly higher in females compared to males, in both mice and human BALF. We also showed specific sex-related differences between murine and human samples. For example, allergen-driven increase in S100A8 and S100A9 was significantly higher in BALF of females compared to males in mice, but significantly higher in males compared to females in humans. Overall, this study provides sex-specific protein biomarkers that are enhanced in response to allergen in murine and human lungs, informing and motivating translational research in allergic asthma.
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spelling pubmed-92738542022-07-13 Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs Hemshekhar, Mahadevappa Mostafa, Dina H. D. Spicer, Victor Piyadasa, Hadeesha Maestre-Batlle, Danay Bolling, Anette K. Halayko, Andrew J. Carlsten, Christopher Mookherjee, Neeloffer Front Immunol Immunology Biological sex influences disease severity, prevalence and response to therapy in allergic asthma. However, allergen-mediated sex-specific changes in lung protein biomarkers remain undefined. Here, we report sex-related differences in specific proteins secreted in the lungs of both mice and humans, in response to inhaled allergens. Female and male BALB/c mice (7-8 weeks) were intranasally challenged with the allergen house dust mite (HDM) for 2 weeks. Bronchoalveolar lavage fluid (BALF) was collected 24 hour after the last HDM challenge from allergen-naïve and HDM-challenged mice (N=10 per group, each sex). In a human study, adult participants were exposed to nebulized (2 min) allergens (based on individual sensitivity), BALF was obtained after 24 hour (N=5 each female and male). The BALF samples were examined in immunoblots for the abundance of 10 proteins shown to increase in response to allergen in both murine and human BALF, selected from proteomics studies. We showed significant sex-bias in allergen-driven increase in five out of the 10 selected proteins. Of these, increase in eosinophil peroxidase (EPX) was significantly higher in females compared to males, in both mice and human BALF. We also showed specific sex-related differences between murine and human samples. For example, allergen-driven increase in S100A8 and S100A9 was significantly higher in BALF of females compared to males in mice, but significantly higher in males compared to females in humans. Overall, this study provides sex-specific protein biomarkers that are enhanced in response to allergen in murine and human lungs, informing and motivating translational research in allergic asthma. Frontiers Media S.A. 2022-06-28 /pmc/articles/PMC9273854/ /pubmed/35837410 http://dx.doi.org/10.3389/fimmu.2022.923986 Text en Copyright © 2022 Hemshekhar, Mostafa, Spicer, Piyadasa, Maestre-Batlle, Bolling, Halayko, Carlsten and Mookherjee https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hemshekhar, Mahadevappa
Mostafa, Dina H. D.
Spicer, Victor
Piyadasa, Hadeesha
Maestre-Batlle, Danay
Bolling, Anette K.
Halayko, Andrew J.
Carlsten, Christopher
Mookherjee, Neeloffer
Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs
title Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs
title_full Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs
title_fullStr Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs
title_full_unstemmed Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs
title_short Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs
title_sort sex dimorphism of allergen-induced secreted proteins in murine and human lungs
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273854/
https://www.ncbi.nlm.nih.gov/pubmed/35837410
http://dx.doi.org/10.3389/fimmu.2022.923986
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