Article
Biochemistry & Molecular Biology
Hazel Dunbar, Ian J. Hawthorne, Courteney Tunstead, Michelle E. Armstrong, Seamas C. Donnelly, Karen English
Summary: Macrophage migration inhibitory factor (MIF) expression is affected by a functional promoter polymorphism, with the number of CATT repeats correlating to MIF expression level. In a pre-clinical model of allergic asthma, mice with increasing CATT repeats (CATT(5) and CATT(7)) showed varying degrees of airway inflammation. The potent MIF inhibitor SCD-19 was able to mitigate the pathophysiology observed in CATT(7) mice, indicating the important role of endogenous human MIF expression in airway inflammation severity.
Article
Biochemistry & Molecular Biology
Hazel Dunbar, Ian J. Hawthorne, Courteney Tunstead, Michelle E. Armstrong, Seamas C. Donnelly, Karen English
Summary: The expression of macrophage migration inhibitory factor (MIF) is controlled by a functional promoter polymorphism, where the number of tetranucleotide repeats (CATTn) corresponds to the level of MIF expression. Using a pre-clinical model of allergic asthma, novel humanized MIF mice with increasing CATT repeats (CATT5 and CATT7) were employed to study airway inflammation. The results showed that high expression of human MIF in CATT7 mice led to a severe asthma phenotype, which could be mitigated by the MIF inhibitor SCD-19. This study provides a reproducible model for studying asthma airway remodeling and suggests a potential role of MIF in driving this process.
Article
Respiratory System
Tsutomu Saito, Tomohiro Ichikawa, Tadahisa Numakura, Mitsuhiro Yamada, Akira Koarai, Naoya Fujino, Koji Murakami, Shun Yamanaka, Yusaku Sasaki, Yorihiko Kyogoku, Koji Itakura, Hirohito Sano, Katsuya Takita, Rie Tanaka, Tsutomu Tamada, Masakazu Ichinose, Hisatoshi Sugiura
Summary: This study found that PGC-1 alpha is involved in the disruption of airway barrier function induced by aeroallergens through the PAR2/TLR4 pathway. Modulation of this pathway could be a novel approach for asthma treatment.
RESPIRATORY RESEARCH
(2021)
Article
Immunology
Verena M. Merk, Truong San Phan, Alice Wiedmann, Rowan S. Hardy, Gareth G. Lavery, Thomas Brunner
Summary: The local synthesis of glucocorticoids in the lung plays an important role in the regulation of allergic airway inflammation, particularly in HDM-induced airway hypersensitivity, by controlling Toll-like receptor 4 signaling and cytokine/chemokine secretion to influence Th17-type immune response.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Respiratory System
Laura Tamasauskiene, Brigita Sitkauskiene
Summary: The study evaluated the cytokine profile, vitamin D status, symptom score, and quality of life in patients with persistent allergic airway diseases sensitized to house dust mites. Novel cytokines such as IL-22, IL-17, and IL-33, as well as vitamin D, may play a role in the pathogenesis of airway inflammation in patients sensitized to HDM.
BMC PULMONARY MEDICINE
(2021)
Article
Allergy
Saliha Ait Yahia, Camille Audousset, Daniel Alvarez-Simon, Han Vorng, Dieudonnee Togbe, Philippe Marquillies, Myriam Delacre, Stephanie Rose, Helene Bouscayrol, Aline Rifflet, Valerie Quesniaux, Ivo Gomperts Boneca, Mathias Chamaillard, Anne Tsicopoulos
Summary: The study found that NOD1-dependent sensing of gram-negative bacteria associated with HDM exacerbates the severity of experimental asthma, suggesting that inhibiting the NOD1 signaling pathway may be a therapeutic approach to treating asthma.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Allergy
Erika Mendez-Enriquez, Perla Abigail Alvarado-Vazquez, Willem Abma, Oscar E. Simonson, Sergey Rodin, Thorsten B. Feyerabend, Hans-Reimer Rodewald, Andrei Malinovschi, Christer Janson, Mikael Adner, Jenny Hallgren
Summary: This study found that mast cells release serotonin, which enhances bronchoconstriction and AHR. Mast cells play a key role in the pathogenesis of asthma, and M3-directed treatments may also act by targeting mast cells.
Article
Immunology
Meixuan Liu, Mengtian Shan, Yunxuan Zhang, Zhongliang Guo
Summary: The study demonstrates that PGRN protects against asthmatic airway remodeling by negatively regulating autophagy via HMGB1 suppression. This finding provides new insights into therapeutic options for HDM-induced chronic asthma.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Allergy
Theresa Walsemann, Marisa Boettger, Stephan Traidl, Christian Schwager, Askin Guelsen, Sina Freimooser, Lennart Matthias Roesner, Thomas Werfel, Uta Jappe
Summary: This study investigates the association between various house dust mite allergens and allergic rhinitis, allergic asthma, and atopic dermatitis, aiming to identify potential biomarkers and improve diagnostics. The results show that sensitization to more than three mite allergens is associated with allergic asthma and/or atopic dermatitis. Certain allergens (Der p 5, Der p 20, and Der p 21) are more closely related to these conditions.
Article
Medicine, Research & Experimental
Ki-Shuk Shim, Hyun-Kyung Song, Youn-Hwan Hwang, Sungwook Chae, Ho Kyoung Kim, Seol Jang, Yun Hee Kim, Byung-Kil Choo, Won-Kyung Yang, Seung-Hyung Kim, Taesoo Kim, Ki Mo Kim
Summary: The ethanol extract of Veronica persica (EEVP) has shown pharmacological activity in suppressing airway inflammation. It effectively inhibits the expression of inflammatory factors, reduces eosinophil infiltration, and decreases the production of cytokines in the lungs and BALF. Furthermore, it suppresses MCP-1 production in bronchial/tracheal epithelial cells by inhibiting STAT-3/6 activation.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Allergy
Huey-Jy Huang, Yvonne Resch-Marat, Anne Casset, Margit Weghofer, Petra Zieglmayer, Rene Zieglmayer, Patrick Lemell, Friedrich Horak, Kuan-Wei Chen, Ekaterina Potapova, Paolo M. Matricardi, Gabrielle Pauli, Monika Grote, Rudolf Valenta, Susanne Vrtala
Summary: Der p 37, a new Dp allergen recognized by a third of HDM-allergic patients, may serve as a surrogate marker for severe HDM sensitization and asthma.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Angelica Papanicolaou, Hao Wang, Jonathan McQualter, Christian Aloe, Stavros Selemidis, Catherine Satzke, Ross Vlahos, Steven Bozinovski
Summary: Allergic airway disease diminishes the control of pneumococcal lung infections, and exposure to house dust mites exacerbates the immune response, leading to more severe infections and increased airway hyperresponsiveness.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Meixuan Liu, Jingjing Lu, Qian Zhang, Yunxuan Zhang, Zhongliang Guo
Summary: This study demonstrates that CC16 can alleviate HDM-induced airway inflammation and damage by inhibiting airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting CC16 as a potential protective option for HDM-induced asthma.
MOLECULAR MEDICINE
(2021)
Article
Immunology
Mirela Curin, Huey-Jy Huang, Tetiana Garmatiuk, Sandra Gutfreund, Yvonne Resch-Marat, Kuan-Wei Chen, Kerstin Fauland, Walter Keller, Petra Zieglmayer, Rene Zieglmayer, Patrick Lemell, Friedrich Horak, Wolfgang Hemmer, Margarete Focke-Tejkl, Sabine Flicker, Susanne Vrtala, Rudolf Valenta
Summary: The study found that Der p 7 has high allergenic activity comparable to other allergens, but did not show any IgE reactivity or allergenic activity in HDM-allergic patients, indicating a lack of sequential IgE epitopes on Der p 7. Through IgE inhibition experiments and molecular modeling, discontinuous, conformational IgE epitopes of Der p 7 were identified.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Food Science & Technology
Sara Benede, Leticia Perez-Rodriguez, Monica Martinez-Blanco, Elena Molina, Rosina Lopez-Fandino
Summary: Orally administered HDM can promote inflammatory and type 2 responses in the intestine, affecting the expression of genes encoding tight junction proteins and cytokines, and activating innate immune cells. However, there is no evidence of HDM promoting sensitization to coadministered proteins in our experimental setting.
Review
Biotechnology & Applied Microbiology
Neeloffer Mookherjee, Marilyn A. Anderson, Henk P. Haagsman, Donald J. Davidson
NATURE REVIEWS DRUG DISCOVERY
(2020)
Article
Chemistry, Multidisciplinary
Thomas H. Mahood, Christopher D. Pascoe, Tobias K. Karakach, Aruni Jha, Sujata Basu, Peyman Ezzati, Victor Spicer, Neeloffer Mookherjee, Andrew J. Halayko
Summary: Analysis of proteomes from lung tissues and BALF of allergen-challenged mice revealed greater diversity in proteins between lung tissues and BALF compared to changes induced by allergen challenge. Biological pathways enriched after allergen exposure were compartment-dependent, with lung tissues showing innate immune responses and oxidative stress, and BALF showing changes in metabolism. Integration of proteomes from different compartments highlighted redox pathways and new proteins that may mediate interactions between lung tissue and BALF after allergen challenge.
Article
Chemistry, Medicinal
Hadeesha Piyadasa, Mahadevappa Hemshekhar, Natasha Osawa, Dylan Lloyd, Anthony Altieri, Sujata Basu, Oleg Krokhin, Andrew J. Halayko, Neeloffer Mookherjee
Summary: Research demonstrates the importance of the tryptophan (W8) in the central hydrophobic region of IDR-1002 for its immunomodulatory activities in both murine and human models. This study provides insights for the design of targeted IDR peptides with specific impact on immunomodulation and respiratory diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Critical Care Medicine
Andrew J. Halayko, Christopher D. Pascoe, Jessica D. Gereige, Michael C. Peters, Robyn T. Cohen, Prescott G. Woodruff
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Cell Biology
Pawan Sharma, Javad Alizadeh, Maya Juarez, Afshin Samali, Andrew J. Halayko, Nicholas J. Kenyon, Saeid Ghavami, Amir A. Zeki
Summary: The study found that cell stress markers in lung tissue of IPF patients are associated with lung function deficits, with co-localization of UPR and autophagy markers positively correlated with increased lung function.
Article
Physiology
Christopher D. Pascoe, Neilloy Roy, Emily Turner-Brannen, Alexander Schultz, Jignesh Vaghasiya, Amir Ravandi, Andrew J. Halayko, Adrian R. West
Summary: Oxidative stress induced by OxPCs impairs epithelial cell function and barrier integrity, contributing to the pathological features of asthma. Mitochondrial dysfunction, lipid peroxidation, and reactive oxygen species generation are involved in a self-propagating cycle of pathological lipid metabolism. Antioxidant N-acetyl cysteine can partially restore cell function.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Physiology
Christopher D. Pascoe, Sujata Basu, Jacquie Schwartz, Mario Fonseca, Shana Kahnamoui, Aruni Jha, Vernon Dolinsky, Andrew J. Halayko
Summary: Exposure to maternal diabetes may have different effects on lung health and airway inflammation in children, with female offspring being more susceptible to inflammatory lung conditions such as asthma, while male offspring display changes more characteristic of chronic obstructive pulmonary disease models.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Physiology
Jeffrey D. Ritzenthaler, Edilson Torres-Gonzalez, Yuxuan Zheng, Igor N. Zelko, Victor van Berkel, David R. Nunley, Biniam Kidane, Andrew J. Halayko, Ross Summer, Walter H. Watson, Jesse Roman
Summary: Old lung fibroblasts exhibit a profibrotic and senescence phenotype, which can be modulated by manipulating the Slc7a11 gene.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Immunology
Amena Aktar, Lianyu Shan, Latifa Koussih, Mohamed S. Almiski, Sujata Basu, Andrew Halayko, Ifeoma Okwor, Jude E. Uzonna, Abdelilah S. Gounni
Summary: The Sema3E/plexinD1 signaling pathway in interstitial macrophages regulates airway inflammation, airway resistance, and tissue remodeling in house dust mite-induced allergic asthma. Reduced IL-10 expression by plexinD1-deficient macrophages may contribute to the exacerbation of these allergic asthma features.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Environmental Sciences
Neeloffer Mookherjee, Min Hyung Ryu, Mahadevappa Hemshekhar, Juma Orach, Victor Spicer, Christopher Carlsten
Summary: This study details the impact of traffic-related air pollution on the human plasma proteome. It identifies specific proteins related to atherosclerosis that increase in concentration as the level of traffic-related air pollution increases.
ENVIRONMENTAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Julia Frankenberg Garcia, Andrew Rogers, Judith C. W. Mak, Andrew J. Halayko, Christopher K. M. Hui, Bingling Xu, Kian Fan Chung, Tristan Rodriguez, Charalambos Michaeloudes, Pankaj K. Bhavsar
Summary: Mitochondrial transfer from mesenchymal stem cells to airway smooth muscle cells can attenuate oxidative stress-induced damage in COPD. However, it is not known whether structural cells in the lungs can also exchange mitochondria and what role this plays in modulating bioenergetics and cellular function. Here, researchers found that airway smooth muscle cells in both healthy ex-smokers and COPD patients can exchange mitochondria, partially through extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and increases mitochondrial donation by the smooth muscle cells, suggesting it may be a stress response mechanism. Moreover, the study showed that the received mitochondria enhance mitochondrial biogenesis and respiration while reducing cell proliferation in healthy ex-smoker airway smooth muscle cells.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Respiratory System
Juma Orach, Christopher Francis Rider, Agnes Che Yan Yuen, Carley Schwartz, Neeloffer Mookherjee, Christopher Carlsten
Summary: In this study, the concentration-response relationship between airway health measures and diesel exhaust exposure was investigated. The results showed that diesel exhaust exposure led to a concentration-dependent increase in airway inflammation, indicating that it may be a sensitive marker of acute inflammatory response in the airways. Furthermore, this study documented the concentration-response estimates of particulate matter <2.5 μm in aerodynamic diameter at exposure levels commonly experienced in the community and occupational settings.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
Article
Rheumatology
Mahadevappa Hemshekhar, Vidyanand Anaparti, Hani El-Gabalawy, Neeloffer Mookherjee
Summary: The combination of highly bioavailable curcumin, vitamin D-3, and omega-3 fatty acids significantly delays and reduces the development of collagen-induced arthritis (CIA). This study suggests a rationale for systematically evaluating these widely available supplements in individuals at risk for developing rheumatoid arthritis.
ARTHRITIS RESEARCH & THERAPY
(2021)