Article
Allergy
Alexis Celle, Pauline Esteves, Guillaume Cardouat, Fabien Beaufils, Edmee Eyraud, Isabelle Dupin, Elise Maurat, Sabrina Lacomme, Olga Ousova, Hugues Begueret, Matthieu Thumerel, Roger Marthan, Pierre-Olivier Girodet, Patrick Berger, Thomas Trian
Summary: This study demonstrates a novel mechanism of bronchial smooth muscle (BSM) remodeling in patients with severe asthma following rhinovirus (RV) exacerbation. The specific migration of BSM cells towards RV-infected bronchial epithelium (BE) is driven by the chemokine ligand C-X-C motif chemokine ligand 10. Decreased expression and activation of the CXCR3-B-specific isoform in BSM cells from patients with severe asthma contribute to this mechanism. These findings highlight the potential therapeutic target of the C-X-C motif chemokine ligand 10/CXCR3-A axis in severe asthma.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
An-nan Zhang, Nan Li, Zhuo-chang Chen, Ya-li Guo, Cui-jie Tian, Dong-jun Cheng, Xue-yi Tang, Xiao-yu Zhang
Summary: Objective of this study was to investigate the effect of amygdalin, an active ingredient in bitter almonds, on TGF-beta-induced EMT in bronchial epithelial cells and elucidate the underlying mechanisms. The results showed that amygdalin treatment relieved airway wall remodeling and decreased the expressions of EMT markers. Furthermore, amygdalin inhibited TGF-beta-induced EMT through regulating the expression of HPSE.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Environmental Sciences
Jianhong Ge, Hongqian Chu, Qianqian Xiao, Weidong Hao, Jing Shang, Tong Zhu, Zhaogang Sun, Xuetao Wei
Summary: Black carbon (BC) reacts with different substances to form aged black carbon, which causes inflammation and lung damage. Both BC and aged BC can enhance the expression of IL-33, but epithelial cells are unlikely to be the source of lung inflammation caused by elevated IL-33 in BC and aged BC. MAPKs and PI3K/AKT pathways are involved in the elevation of IL-33.
ENVIRONMENTAL POLLUTION
(2021)
Article
Allergy
Alexandra Schroeder, Lars P. Lunding, Ulrich M. Zissler, Christina Vock, Sina Webering, Johanna C. Ehlers, Zane Orinska, Adam Chaker, Carsten B. Schmidt-Weber, Niklas J. Lang, Herbert B. Schiller, Marcus A. Mall, Heinz Fehrenbach, Charles A. Dinarello, Michael Wegmann
Summary: The study found that IL-37 downregulates allergic airway inflammation by counterbalancing the disease-amplifying effects of IL-1 beta and IL-33.
Article
Respiratory System
Sam Strickson, Kirsty F. Houslay, Victor A. Negri, Yoichiro Ohne, Tomas Ottosson, Roger B. Dodd, Catherine Chaillan Huntington, Tina Baker, Jingjing Li, Katherine E. Stephenson, Andy J. O'Connor, J. Sophie Sagawe, Helen Killick, Tom Moore, D. Gareth Rees, Sofia Koch, Caroline Sanden, Yixin Wang, Elise Gubbins, Mahboobe Ghaedi, Roland Kolbeck, Saumyaa Saumyaa, Jonas S. Erjefalt, Gary P. Sims, Alison A. Humbles, Ian C. Scott, Xavier Romero Ros, E. Suzanne Cohen
Summary: This study reveals that IL-33, RAGE, and EGFR act together in an ST2-independent pathway in the airway epithelium, governing abnormal epithelial remodeling and mucus-obstructive features in COPD.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Courtney Marshall, Mahadevappa Hemshekhar, Dylan Lloyd, Neeloffer Mookherjee
Summary: IL-33 is an alarmin produced by stromal cells that promotes airway inflammation and plays a critical role in severe asthma. This study reveals that the aryl hydrocarbon receptor (AhR) is involved in the cytokine-mediated IL-33 production, specifically in the presence of IFN gamma. Knockdown of AhR leads to a significant decrease in IFN gamma-induced IL-33 production and phosphorylation of STAT1 (Y701) in human bronchial epithelial cells.
Article
Environmental Sciences
Xin Fu, Wei Hong, Shuyi Li, Zhi Chen, Wenqu Zhou, Jianwei Dai, Xiaoliang Deng, Hongbin Zhou, Bing Li, Pixin Ran
Summary: The study reveals that biofuel PM2.5 can induce significant pyroptosis and inflammation in human bronchial epithelial cells through both classic NLRP3/Caspase-1/IL-1 beta-dependent and novel ATP/P2Y-dependent mechanisms.
Article
Biotechnology & Applied Microbiology
Yumei Ren, Yongbin Yan, Lei Zhen, Caihong Cao, Quan Wang, Yingying Zhang, Shan Zhu
Summary: The study aimed to investigate the effects and action mechanism of Zhike Pingchuan Granule in human bronchial epithelial cells induced by IL-6 or the supernatant of M2. Results showed that ZKPC disrupted important IL-6 inducible genes related to apoptosis, oxidative, and inflammatory responses, which was enhanced by JAK2 inhibitor. Additionally, ZKPC inhibited the IL-6-induced JAK2/STAT3 signaling cascade, increased cell viability, and decreased apoptosis in human bronchial epithelial cells cultured in the supernatant of M2.
Article
Medicine, Research & Experimental
Ella Katz-Kiriakos, Deborah F. Steinberg, Colin E. Kluender, Omar A. Osorio, Catie Newsom-Stewart, Arjun Baronia, Derek E. Byers, Michael J. Holtzman, Dawn Katafiasz, Kristina L. Bailey, Steven L. Brody, Mark J. Miller, Jennifer Alexander-Brett
Summary: The study revealed that IL-33 secretion relies on the nSMase2-regulated multivesicular endosome (MVE) pathway and is cosecreted with exosomes as surface-bound cargo. COPD patients showed increased secretion of IL-33 isoforms and elevated nSMase2 expression, providing potential therapeutic targets for chronic airway diseases driven by type 2 inflammation.
Article
Virology
Charlene Akoto, Anna Willis, Chiara F. Banas, Joseph A. Bell, Dean Bryant, Cornelia Blume, Donna E. Davies, Emily J. Swindle
Summary: In this study, the researchers investigated the response of mast cells (MCs) to IL-33 stimulation and found that it increased the susceptibility of MCs to HRV infection through upregulation of ICAM1. This highlights a potential gene-environment interaction that could contribute to virus-induced asthma exacerbations.
Article
Pharmacology & Pharmacy
Stanislav Kan, Christopher Grainge, Kristy Nichol, Andrew Reid, Darryl Knight, Yong Sun, Nathan Bartlett, Mingtao Liang
Summary: This study developed nanoparticles for targeted delivery of TLR7 agonist to airway epithelial cells, which showed enhanced innate immune activation and suppression of viral replication.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Mei-Lan Tsai, Ming-Kai Tsai, Yi-Giien Tsai, Yu-Chih Lin, Ya-Ling Hsu, Yi-Ting Chen, Yi-Ching Lin, Chih-Hsing Hung
Summary: This study investigated the effects of LTRAs on the expression of epithelium-derived cytokines in human airway epithelial cells and explored the underlying intracellular processes, including epigenetic regulation. It was found that LTRAs might induce the production of IL-25, IL-33, and TSLP by activating the MAPK and NF-kappa B pathways and regulating histone H3 acetylation and H3K36 and H3K79 trimethylation, exacerbating inflammation and asthma symptoms. Therefore, LTRA monotherapy may not be an appropriate therapeutic option for asthma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Yanbo Wang, Yanling Yu, Wanjing Yu, Xun Bian, Linxia Gong
Summary: IL-35 inhibits cell pyroptosis and reduces asthma injury by suppressing the p38 MAPK pathway.
Article
Allergy
Yuying Huang, Xuezhen Li, Lin Zhu, Chunrong Huang, Wen Chen, Zhiyang Ling, SongLing Zhu, Xintong Feng, Chunyan Yi, Wangpeng Gu, Chenghua Yan, Jing Wang, Liyan Ma, Xiao Su, Ranran Dai, Guochao Shi, Bing Sun, Yaguang Zhang
Summary: The study discovered that by inhibiting thrombin, the maturation of IL-33 can be regulated, thus impacting ILC2s cells and treating lung inflammation.
Article
Critical Care Medicine
Xingnan Li, Stefano Guerra, Julie G. Ledford, Monica Kraft, Huashi Li, Annette T. Hastie, Mario Castro, Loren C. Denlinger, Serpil C. Erzurum, John Fahy, Benjamin Gaston, Elliot Israel, Nizar N. Jarjour, Bruce D. Levy, David T. Mauger, Wendy C. Moore, Joe Zein, Naftali Kaminski, Sally E. Wenzel, Prescott G. Woodruff, Deborah A. Meyers, Eugene R. Bleecker
Summary: This study investigated the association between CC16 mRNA expression levels in nonciliated bronchial epithelial cells (BECs) and asthma severity. The results showed that low CC16 mRNA expression levels were significantly associated with asthma susceptibility, severity, exacerbations, and T2 inflammation biomarkers. Additionally, CC16 mRNA expression levels were correlated with the expression levels of Th2, Th1, and inflammation genes. A combination of CC16 and IL-6 could identify different asthma endotypes.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Immunology
Sangeetha Ramu, Hamid Akbarshahi, Sofia Mogren, Frida Berlin, Samuel Cerps, Mandy Menzel, Morten Hvidtfeldt, Celeste Porsbjerg, Lena Uller, Cecilia K. Andersson
Summary: The study revealed that stimulation with MC proteases can induce the release of inflammatory mediators and alarmins from human bronchial epithelial cells, while also decreasing anti-viral responses. Furthermore, MC proteases lead to downregulation of epithelial junction proteins, potentially causing barrier dysfunction.
Article
Immunology
Mandy Menzel, Hamid Akbarshahi, Irma Mahmutovic Persson, Cecilia Andersson, Manoj Puthia, Lena Uller
Summary: Asthma exacerbations are often triggered by rhinovirus infections, which activate the NF kappa B pathway leading to airway inflammation and increased Th2 cytokine expression. This study using a mouse model demonstrates that NF kappa B signaling is involved in impaired IFN beta production during viral-induced asthma exacerbations. Lack of NF kappa B1 results in lower IL-33 levels and reduced eosinophilia after allergen challenge, but enhanced expression of IFN beta and antiviral proteins at exacerbation. These findings suggest a potential therapeutic target in targeting NF kappa B pathways during viral infection-induced exacerbations.
JOURNAL OF INNATE IMMUNITY
(2022)
Article
Allergy
Samuel Cerps, Asger Sverrild, Sangeetha Ramu, Juan Jose Nieto-Fontarigo, Hamid Akbarshahi, Mandy Menzel, Cecilia Andersson, Sofia Tillgren, Morten Hvidtfeldt, Celeste Porsbjerg, Lena Uller
Summary: This study found that exposure to house dust mite (HDM) affected the anti-viral and anti-bacterial responses in airway epithelial cells of allergic asthma patients, potentially leading to asthma exacerbations. However, HDM exposure did not affect the release of TSLP, a driver of T2 inflammation.
Article
Immunology
Juan Jose Nieto-Fontarigo, Sofia Tillgren, Samuel Cerps, Asger Sverrild, Morten Hvidtfeldt, Sangeetha Ramu, Mandy Menzel, Adam Frederik Sander, Celeste Porsbjerg, Lena Uller
Summary: Imiquimod reduces ACE2 expression and pro-inflammatory cytokines, increases IFN-beta expression in HBECs, potentially improving viral infection tolerance in asthmatic patients. The data suggest the feasibility of developing pluripotent drugs for anti-viral treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sofia Malm Tillgren, Juan Jose Nieto-Fontarigo, Samuel Cerps, Sangeetha Ramu, Mandy Menzel, Irma Mahmutovic Persson, Anja Meissner, Hamid Akbarshahi, Lena Uller
Summary: The genetic background of mice has a significant impact on the lung inflammatory response to synthetic dsRNA. BALB/c and C57Bl/6J mice showed stronger inflammatory response to dsRNA, while C57Bl/6N mice exhibited a weaker response.
JOURNAL OF INFLAMMATION-LONDON
(2023)
Article
Allergy
A. Sverrild, S. Cerps, J. J. Nieto-Fontarigo, S. Ramu, M. Hvidtfeldt, M. Menzel, J. Kearley, J. M. Griffiths, J. R. Parnes, C. Porsbjerg, L. Uller
Summary: Blocking TSLP in asthma patients reduces airway epithelial inflammatory response to viral challenge without affecting anti-viral host resistance.
Article
Allergy
Veronika Mraz, Rebecca K. D. Lohmann, Mandy Menzel, Alana Hawkes, Helen Vaher, Anders B. Funch, Mia H. Jee, Anne-Sofie o. Gadsboll, Julie F. Weber, Kelvin Yeung, Niels Odum, Anders Woetmann, Dianne Mckay, Deborah Witherden, Carsten Geisler, Charlotte M. Bonefeld
Summary: This study reveals the central role of JAML in CHS and suggests a potential new target for the treatment of ACD in humans.
CONTACT DERMATITIS
(2023)
Article
Allergy
Mandy Menzel, Veronika Mraz, Helen Vaher, Carsten Geisler, Charlotte Menne Bonefeld
Summary: Allergic contact dermatitis (ACD) is a common skin disease characterized by metabolic re-programming. Exposure to contact allergens causes various metabolic alterations.
CONTACT DERMATITIS
(2023)
Meeting Abstract
Respiratory System
S. Tillgren, S. Cerps, M. Menzel, I. Mahmutovic Persson, J. J. Nieto Fontarigo, H. Akbarshahi, L. Uller
EUROPEAN RESPIRATORY JOURNAL
(2022)
Meeting Abstract
Surgery
Sandra Lindstedt, Edgars Grins, Johan Nilsson, Hamid Akbarshahi, Johan Sjoren, Snejana Hyllen, Lennart Hansson, Hillevi Larsson, Per Ederoth, Ronny Gustafsson
TRANSPLANT INTERNATIONAL
(2021)
Meeting Abstract
Respiratory System
Juan-Jose Nieto-Fontarigo, Samuel Cerps, Sangeetha Ramu, Hamid Akbarshahi, Asger Sverrild, Celeste Porsbjerg, Uller Lena
EUROPEAN RESPIRATORY JOURNAL
(2020)
Meeting Abstract
Respiratory System
Samuel Cerps, Hamid Akbarshahi, Sangeetha Ramu, Mandy Menzel, Cecilia Andersson, Morten Hvidtfeldt, Asger Sverrild, Celeste Porsbjerg, Lena Uller
EUROPEAN RESPIRATORY JOURNAL
(2020)