Article
Biochemistry & Molecular Biology
Yukitomo Arao, Deborah J. J. Stumpo, Mark J. J. Hoenerhoff, Robert M. M. Tighe, Yen-Rei Yu, Deloris Sutton, Amogh Kashyap, Isabel Beerman, Perry J. J. Blackshear
Summary: GM-CSF is a cytokine that promotes the growth and differentiation of granulocyte and macrophage precursors. The stability of Csf2 mRNA is regulated by an adenine-uridine-rich element (ARE) in its 3' untranslated region. Knockout mice lacking this ARE showed increased stability of Csf2 mRNA and elevated levels of GM-CSF, leading to severe respiratory distress and death. This suggests that post-transcriptional regulation of Csf2 mRNA stability is essential for normal GM-CSF secretion and pulmonary macrophage homeostasis.
Article
Biochemistry & Molecular Biology
Yukitomo Arao, Deborah J. Stumpo, Mark J. Hoenerhoff, Robert M. Tighe, Yen-Rei Yu, Deloris Sutton, Amogh Kashyap, Isabel Beerman, Perry J. Blackshear
Summary: The adenine-uridine-rich element (ARE) found in the Csf2 mRNA of mice is crucial for the stability of the transcript and plays a vital role in the regulation of GM-CSF secretion and pulmonary macrophage homeostasis. Mice with a knock-in deletion of the 75-nucleotide ARE developed severe respiratory distress and exhibited lung abnormalities, indicating the importance of this element in normal lung function.
Article
Medicine, Research & Experimental
Tarani Kanta Barman, Amit K. Singh, Jesse L. Bonin, Tanvir Noor Nafiz, Sharon L. Salmon, Dennis W. Metzger
Summary: This study found that coinfection of SARS-CoV-2 and Streptococcus pneumoniae leads to lung inflammation and death, and the treatment methods differ. Treatment with murine GM-CSF can reduce bacteria and pathology, partially protecting from death, but therapeutic targeting of IFNs does not work. Combined vaccination provides 100% protection against subsequent coinfection.
Article
Immunology
Thomas Belcher, Hana Kammoun, Loic Coutte, Anne-Sophie Debrie, Nathalie Mielcarek, Jean-Claude Sirard, Stephane Cauchi, Camille Locht
Summary: This study demonstrates that the live attenuated vaccine BPZE1 provides protection against an unrelated bacterial pathogen, Streptococcus pneumoniae, in a mouse model of invasive pneumococcal disease. The protection is linked to live vaccination and the role of the innate immune system.
Article
Pharmacology & Pharmacy
Shisong Jing, Li Wang, Tiedong Wang, Lianghai Fan, Lin Chen, Hua Xiang, Yan Shi, Dacheng Wang
Summary: The study identified a compound named myricetin that effectively inhibits the activity of ClpP, reduces the pathogenicity of Staphylococcus aureus in vivo, enhances the efficacy of traditional antibiotics against MRSA, and protects mice from fatal lung infections caused by MRSA.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Douglas Borges de Figueiredo, Kan Kaneko, Tasson da Costa Rodrigues, Ronan MacLoughlin, Eliane Namie Miyaji, Imran Saleem, Viviane Maimoni Goncalves
Summary: Pneumococcal disease is a global burden, and the current vaccines are becoming less effective due to serotype replacement. This study investigated the use of polymeric nanoparticles to deliver PspA, a candidate for new pneumococcal vaccines, and found that PGA-co-PDL/HCl-CS or PLGA/HCl-CS nanoparticles with encapsulated or adsorbed PspA provided serotype-independent protection.
Article
Immunology
Fatemeh Korpi, Gholamreza Irajian, Fatemeh Forouhi, Taher Mohammadian
Summary: The study shows that a chimeric vaccine including PcrV, FlaA, FlaB, and OprF (PABF) protein can induce a robust immune response, reduce bacterial burden, and improve survival after P. aeruginosa infection. It exhibits broad-spectrum immunity and holds promise as a candidate for treating and controlling P. aeruginosa infections.
MICROBIAL PATHOGENESIS
(2023)
Article
Physiology
Satoshi Okamori, Makoto Ishii, Takanori Asakura, Shoji Suzuki, Ho Namkoong, Shizuko Kagawa, Ahmed E. Hegab, Kazuma Yagi, Hirofumi Kamata, Tatsuya Kusumoto, Takunori Ogawa, Hayato Takahashi, Masaki Yoda, Keisuke Horiuchi, Naoki Hasegawa, Koichi Fukunaga
Summary: The study showed that ADAM10 plays a protective role in regulating influenza virus infection and may be a potential therapeutic target.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Immunology
Patricia Perez, David Astorgano, Guillermo Albericio, Sara Flores, Pedro J. Sanchez-Cordon, Joanna Luczkowiak, Rafael Delgado, Jose M. Casasnovas, Mariano Esteban, Juan Garcia-Arriaza
Summary: Intranasal administration of vaccines can induce mucosal and systemic immune responses, protecting animals from SARS-CoV-2 infection and preventing virus transmission.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Renee L. Tonkin, Anna Klockner, Adrian Najer, Carolina J. Simoes da Silva, Cecile Echalier, Marc S. Dionne, Andrew M. Edwards, Molly M. Stevens
Summary: This study develops a hierarchical microparticle system for bacteria-activated single- and dual-antibiotic drug delivery, effectively killing antibiotic-resistant bacteria.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Immunology
Kelly L. Monaghan, Wen Zheng, Halima Akhter, Lei Wang, Amanda G. Ammer, Peng Li, Jian-Xin Lin, Gangqing Hu, Warren J. Leonard, Edwin C. K. Wan
Summary: In immune responses, monocytes have diverse functions such as pathogen clearance and tissue repair. However, abnormal control of monocyte activation can lead to chronic inflammation and tissue damage. This study reveals that GM-CSF-induced STAT5 tetramerization plays a critical role in determining monocyte fate and function. Monocytes require STAT5 tetramers to differentiate into moDCs, while the absence of STAT5 tetramers results in the differentiation into a distinct monocyte-derived macrophage population. In a colitis model, STAT5 tetramer-deficient monocytes worsen disease severity, and this is associated with overexpression of arginase I and reduced nitric oxide synthesis. Inhibition of arginase I and sustained supplementation of nitric oxide ameliorate the worsened colitis in STAT5 tetramer-deficient mice.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Samira Marx, Beate M. Kuemmerer, Christian Grutzner, Hiroki Kato, Martin Schlee, Marcel Renn, Eva Bartok, Gunther Hartmann
Summary: The therapeutic use of the RIG-I activator 3pRNA improves survival and reduces disease severity in mice infected with SARS-CoV-2. Mice treated with 3pRNA show lower viral load, reduced lung inflammation, and develop a specific neutralizing antibody response against SARS-CoV-2.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Mika Yamada, Jinya Suzuki, Satsuki Sato, Yasuo Zenimaru, Rie Saito, Tadashi Konoshita, Fredric B. Kraemer, Tamotsu Ishizuka
Summary: This study demonstrates that overexpression of HSL can restore lipotoxicity in the hearts of ATGL-deficient mice, normalizing cardiac function and structure. These findings highlight the potential of cardiac HSL activation as an effective strategy for treating lipotoxic cardiomyopathy associated with ATGL deficiency.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Immunology
Garrison Cox, Andres J. Gonzalez, Emmanuel C. Ijezie, Andres Rodriguez, Craig R. Miller, James T. Van Leuven, Tanya A. Miura
Summary: Rhinoviruses (RV) can inhibit pulmonary coronavirus infection, reduce inflammation and tissue damage, and prevent mortality. These findings are important for understanding the interaction between respiratory viruses and the host, and their impact on disease pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Hiroo Wada, Masuo Nakamura, Shin-Ichi Inoue, Akihiko Kudo, Tomoko Hanawa, Yoichiro Iwakura, Fumie Kobayashi, Hiroshi Kamma, Shigeru Kamiya, Kazuhiro Ito, Peter J. Barnes, Hajime Takizawa
Summary: The study found that IL-17A and IL-17F play important roles in neutrophilic inflammation observed in COPD and severe asthma. Mice deficient in both Il17a and Il17f showed significantly reduced neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure, indicating that dual IL-17A/F signalling plays a crucial role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure.
SCIENTIFIC REPORTS
(2021)
Article
Critical Care Medicine
Sharon Leung, Stephen M. Pastores, John M. Oropello, Craig M. Lilly, Samuel M. Galvagno, Neeraj Badjatia, Judith Jacobi, Daniel L. Herr, Jason David Oliveira
Summary: This article proposes a framework based on expert opinions and survey responses to assist critical care organizations in designing and implementing successful regionalization. The article highlights the need for a critical assessment of administrative and clinical challenges and barriers, and emphasizes the importance of systems thinking, business planning and control, and essential infrastructure development.
CRITICAL CARE MEDICINE
(2022)
Article
Peripheral Vascular Disease
Emma J. B. Holjak, Iryna Savinova, Victoria L. Nelson, Leslie M. Ogilvie, Anabelle M. Ng, Brittany A. Edgett, Mathew J. Platt, Keith R. Brunt, Kjetil Ask, Jeremy A. Simpson
Summary: The study found that while systolic blood pressure remained consistent, the Spontaneously Hypertensive Rat (SHR) model showed an increase in concentric hypertrophy in terms of heart weight and posterior wall thickness. This cardiac-based phenotypic shift was not observed in the control group, indicating the presence of significant changes in the SHR model.
AMERICAN JOURNAL OF HYPERTENSION
(2022)
Article
Biochemistry & Molecular Biology
Toyoshi Yanagihara, Kazuya Tsubouchi, Mahsa Gholiof, Sy Giin Chong, Kenneth E. Lipson, Quan Zhou, Ciaran Scallan, Chandak Upagupta, Jussi Tikkanen, Shaf Keshavjee, Kjetil Ask, Martin R. J. Kolb
Summary: Idiopathic pulmonary fibrosis is a fatal lung disease characterized by the accumulation of myofibroblasts. The study found that connective-tissue growth factor (CTGF) plays a key role in pulmonary fibrosis. Increased levels of CTGF exacerbate lung fibrosis and CTGF expression is upregulated in patients with idiopathic pulmonary fibrosis. Different cells contribute to the maintenance of the fibrotic phenotype during fibrogenesis.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Sonal R. Pannu, Tyler Haddad, Matthew Exline, John W. Christman, Jeffrey C. Horowitz, Jonathan Peters, Guy Brock, Philip Diaz, Elliott D. Crouser
Summary: This study aims to improve targeted oxygenation in mechanically ventilated patients by reducing excessive FiO(2) exposure. The use of algorithm-based FiO(2) titration and electronic alert system aims to curb hyperoxemia and prevent hypoxemia by shortening the time spent with high FiO(2) levels.
CONTEMPORARY CLINICAL TRIALS
(2022)
Article
Medicine, General & Internal
Stijn E. Verleden, Peter Braubach, Christopher Werlein, Edith Plucinski, Mark P. Kuhnel, Annemiek Snoeckx, Haroun El Addouli, Tobias Welte, Axel Haverich, Florian P. Laenger, Sabine Dettmer, Patrick Pauwels, Veronique Verplancke, Paul E. Van Schil, Therese Lapperre, Johanna M. Kwakkel-Van-Erp, Maximilian Ackermann, Jeroen M. H. Hendriks, Danny Jonigk
Summary: Pathology and radiology are complementary tools in diagnosing non-neoplastic pulmonary diseases. The innovative technique of inflating whole lung specimens and subjecting them to CT allows for an accurate matching of CT imaging and histopathology data. This technique enables targeted assessment of localized disease extent and investigation of early mechanisms of lung diseases on a morphological and molecular level.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Carolin K. Watson, Daniela Schloesser, Katrin Fundel-Clemens, Carmen Lerner, Svenja Gabler, Praveen Baskaran, Christian T. Wohnhaas, Stefanie Dichtl, Heinrich J. Huber, Kjetil Ask, Florian Gantner, Coralie Viollet, Matthew J. Thomas, Fidel Ramirez, Peter J. Murray, Karim C. El Kasmi
Summary: This study aims to identify the phenotypes of profibrotic and prohomeostatic macrophages and discover new therapeutic approaches for fibrotic disease. By combining in vivo and in vitro RNA-sequencing methods, the study found that nintedanib can promote the expression of IL-4/IL-13 pathway genes in lung macrophages, leading to tissue repair.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Immunology
Matthew Hamilton, Victoria Turpin, Anmar Ayoub, Amir Reihani, Jorge Arredondo, Kjetil Ask, David A. Clark, Warren G. Foster
Summary: Estrogen-dependent extrauterine implantation and growth of menstrual endometrial tissue affects approximately 10% of reproductive age women and relies on suppression of local innate immune defenses to prevent ectopic tissue rejection. CD200 and increased expression of CD200R1 may facilitate the development of ectopic deposits by suppressing rejection mechanisms.
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Michael Bonert, Uzma Zafar, Soha Ramadan, Christian Finley, Jean-Claude Cutz, Gary Foster, Kjetil Ask, Asghar Naqvi
Summary: Mediastinal lymph node fine needle aspiration (MLN-FNA) is a common procedure, but the physician factor and anatomical site are not routinely assessed. This study evaluated the bias of pathologists and submitting physicians/surgeons and found that both physician and anatomical site are significant predictors of MLN-FNA pathology.
SCIENTIFIC REPORTS
(2023)
Article
Critical Care Medicine
Toyoshi Yanagihara, Kazuya Tsubouchi, Quan Zhou, Michael Chong, Kohei Otsubo, Takuma Isshiki, Jonas C. Schupp, Seidai Sato, Ciaran Scallan, Chandak Upagupta, Spencer Revill, Anmar Ayoub, Sy Giin Chong, Anna Dvorkin-Gheva, Naftali Kaminski, Jussi Tikkanen, Shaf Keshavjee, Guillaume Pare, Christophe Guignabert, Kjetil Ask, Martin R. J. Kolb
Summary: This study investigated the role of vascular remodeling in fibrotic lungs and its contribution to the progression of fibrosis. It was found that endothelial dysfunction and activation of vascular smooth muscle cells enhance fibrogenesis through impaired BMPR2 signaling. Tacrolimus may have therapeutic potential in treating advanced IPF and concomitant PH. Additionally, genetic abnormalities may determine the development of PH in advanced IPF.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Toyoshi Yanagihara, Quan Zhou, Kazuya Tsubouchi, Spencer Revill, Anmar Ayoub, Mahsa Gholiof, Sy Giin Chong, Anna Dvorkin-Gheva, Kjetil Ask, Wei Shi, Martin RJ. Kolb
Summary: Type 1 alveolar epithelial cells (AT1s) and type 2 alveolar epithelial cells (AT2s) regulate the structural integrity and function of alveoli. Gremlin, an inhibitor of bone morphogenetic protein (BMP), induces AT2 proliferation and differentiation. It was found that Gremlin expression during lung injury leads to inhibition of BMP signaling and activation of AT2s, promoting alveolar repair.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Takuma Isshiki, Megan Vierhout, Safaa Naiel, Pareesa Ali, Parichehr Yazdanshenas, Vaishnavi Kumaran, Zi Yang, Anna Dvorkin-Gheva, Anthony F. Rullo, Martin R. J. Kolb, Kjetil Ask
Summary: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by severe scarring in the lung interstitium. Macrophages play a crucial role in the development of pulmonary fibrosis, and recent studies have revealed the heterogeneity and plasticity of pro-fibrotic macrophages. This review discusses the role and characterization of pro-fibrotic macrophages in fibrotic lung diseases and explores the potential of targeting macrophage polarity as a therapeutic strategy for lung fibrosis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Olivia Mekhael, Spencer D. Revill, Aaron Hayat, Steven P. Cass, Kyle MacDonald, Megan Vierhout, Anmar Ayoub, Amir Reihani, Manreet Padwal, Jewel Imani, Ehab Ayaub, Tamana Yousof, Anna Dvorkin-Gheva, Anthony Rullo, Jeremy A. Hirota, Carl D. Richards, Darren Bridgewater, Martin R. Stampfli, Nathan Hambly, Asghar Naqvi, Martin R. J. Kolb, Kjetil Ask
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with unknown cause, characterized by fibrosis. Macrophage accumulation is involved in the pathogenesis of IPF, and the unfolded protein response (UPR) is linked to macrophage activation. The impact of ATF6a, a mediator of UPR, on pulmonary macrophage composition and function in lung injury and fibrogenesis is unclear. This study found that Atf6a is expressed in pro-fibrotic macrophages in lung tissues of IPF patients and circulating monocytes. Deletion of Atf6a in myeloid cells altered macrophage composition and exacerbates fibrogenesis. Further investigation revealed that ATF6a is required for CHOP induction and macrophage death. These findings indicate a detrimental role for ATF6a-deficient macrophages in lung injury and fibrosis.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Oncology
Maria Eugenia Davola, Olga Cormier, Alyssa Vito, Nader El-Sayes, Susan Collins, Omar Salem, Kjetil Ask, Spencer Revill, Yonghong Wan, Karen Mossman
Summary: Immunotherapy stimulates the patient's immune system to fight cancer, but some tumors are immune cold and do not respond well to immune checkpoint therapies. Oncolytic viruses preferentially target tumor cells and can stimulate immune responses. An oncolytic virus based on a common human herpesvirus has been approved by the FDA and used in cancer immunotherapy. In this study, an oncolytic bovine herpesvirus is shown to activate immune responses in a mouse model, and the addition of low-dose chemotherapy enhances immune responses and enables immune checkpoint therapy to clear tumors.
Article
Allergy
Hyung-Geun Moon, Jacob D. Eccles, Seung-jae Kim, Ki-Hyun Kim, Young-Mee Kim, Jalees Rehman, Hyun Lee, Pinal Kanabar, John W. Christman, Steven J. Ackerman, Christian Ascoli, Homan Kang, Hak Soo Choi, Minhyung Kim, Sungyong You, Gye Young Park
Summary: C1q is selectively enriched in the CSF1R+cDC2 subset among conventional DCs, and it plays a critical role in allergen sensing and allergic lung inflammation. The C1q receptor CD91 (LRP1) is required for lung CSF1R+cDC2s to recognize the C1q-allergen complex and induce allergic lung inflammation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Meeting Abstract
Critical Care Medicine
S. Naiel, N. Dowdall, S. D. Revill, V. Kumaran, A. Hayat, A. Ayoub, P. Ali, Q. Zhou, T. Isshiki, M. Vierhout, A. Dvorkin-Gheva, J. Hu, J. Mahmoudi, E. Wong, R. Couto, B. Yepez, B. Seifried, P. Moquin, M. R. Kolb, T. Hoare, K. Ask
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)