Article
Biochemistry & Molecular Biology
Annett Eitner, Sylvia Mueller, Christian Koenig, Arne Wilharm, Rebecca Raab, Gunther O. Hofmann, Thomas Kamradt, Hans-Georg Schaible
Summary: IL-1 beta induces NO release and mitochondrial dysfunction, and both can be prevented by inhibiting iNOS with L-NIL. Additionally, enhancing cAMP or inhibiting AMPK can reduce the effects of IL-1 beta, preventing NO release and mitochondrial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Josephine Kemna, Evelyne Gout, Leon Daniau, Jessica Lao, Kristoffer Weissert, Sandra Ammann, Ralf Kuehn, Matthias Richter, Christine Molenda, Anje Sporbert, Dario Zocholl, Robert Klopfleisch, Hugues Lortat-Jacob, Peter Aichele, Thomas Kammertoens, Thomas Blankenstein
Summary: The study demonstrates that the extracellular matrix (ECM)-binding domain (EBD) of interferon-gamma (IFN gamma) is crucial for preventing high systemic levels of this cytokine and related immunopathology. Lack of EBD in IFN gamma significantly reduces ECM binding but retains the binding to IFN gamma receptor and bioactivity. Overexpression of EBD-deficient IFN gamma results in increased systemic levels, sickness behavior, weight loss, and toxicity.
Article
Cell Biology
Yan-Lin Chen, De-Yi Yan, Chen-Yu Wu, Jiang-Wei Xuan, Chen-Qiang Jin, Xin-Li Hu, Guo-Dong Bao, Yu-Jie Bian, Zhi-Chao Hu, Zhong-Hai Shen, Wen-Fei Ni
Summary: OA is characterized by destruction of articular cartilage and inflammation plays a key role in its progression. Maslinic acid (MA) from olive fruit has been shown to have anti-inflammatory effects. In in vitro and in vivo experiments, MA was found to attenuate inflammatory mediators and inhibit the progression of OA disease.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Medicine, General & Internal
Qingqing Lu, Zhenhua Zhu, Chaochao Tan, Hui Zhou, Yan Hu, Ge Shen, Pan Zhu, Gang Yang, Xiaobing Xie
Summary: The study found that levels of IL-10, IL-1 beta, MCP-1, TNF-alpha, and IL-4 were significantly higher in COVID-19 patients compared to non-COVID-19 patients, while IL-6 was only significantly higher than in healthy individuals and IP-10 was significantly lower than in patients with other diseases. The detection of these cytokines may assist in the clinical study of COVID-19, and IP-10 could potentially be an early elevation cytokine in COVID-19 patients.
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
(2021)
Article
Immunology
Dorottya Szabo, Pal Tod, Flora Goloncser, Viktor Roman, Balazs Lendvai, Lilla Otrokocsi, Beata Sperlagh
Summary: This study further confirms the involvement of purinergic P2X7 receptors in the development of autism-like features caused by maternal immune activation. The downstream signaling pathways associated with P2X7 are identified, and the use of anti-inflammatory drugs is found to inhibit the development of these autism characteristics. Potential biomarkers and therapeutic targets for autism spectrum disorder are also discovered.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Ariadna Montero-Blay, Javier Delgado Blanco, Irene Rodriguez-Arce, Claire Lastrucci, Carlos Pinero-Lambea, Maria Lluch-Senar, Luis Serrano
Summary: Researchers have developed a non-pathogenic bacterium, Mycoplasma pneumoniae (MPN), for the treatment of lung diseases. By designing a single-chain interleukin-10 (SC-IL10), they were able to significantly increase the expression level of IL-10 in the MPN bacteria, resulting in a powerful anti-inflammatory effect on lung infections.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Cell Biology
Kaiqiang Sun, Jian Zhu, Jingchuan Sun, Xiaofei Sun, Le Huan, Bin Zhang, Feng Lin, Bing Zheng, Jialin Jiang, Xi Luo, Ximing Xu, Jiangang Shi
Summary: The study showed that neuropeptide Y (NPY) can promote nucleus pulposus (NP) cell proliferation, inhibit cell apoptosis, and alleviate degeneration. NPY also reduces extracellular matrix (ECM) degradation in cells. These findings are significant for research on intervertebral disc degeneration.
Article
Food Science & Technology
Anderson Fellyp Avelino Diniz, Brena Freire de Oliveira Claudino, Daiany Maria Claudino Francelino, Edvaldo Balbino Alves Junior, Paula Benvindo Ferreira, Francisco Fernandes Lacerda Junior, Barbara Cavalcanti Barros, Ray Ravilly Alves Arruda, Adriano Francisco Alves, Leonia Maria Batista, Bagnolia Araujo da Silva
Summary: Obesity is an energy imbalance that leads to various pathophysiological conditions, including gastrointestinal diseases, and is associated with overexpression of oxidative stress and pro-inflammatory cytokines. Arthorpira platensis (AP), an alga with anti-inflammatory and antioxidant activities, showed preventive effects on oxidative stress and interleukin-1 & beta; (IL-1 & beta;) levels in the ileum of rats fed a hypercaloric diet. The supplementation of AP prevented underproduction of antioxidant enzymes, overexpression of oxidative stress, and an increase in IL-1 & beta; levels in obese rats, making it a promising therapeutic alternative in the treatment of inflammatory bowel diseases aggravated by obesity.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Biochemistry & Molecular Biology
Boda Chen, Dingchao Zhu, Chenglong Xie, Yifeng Shi, Libin Ni, Huawei Zhang, Sunlong Li, Jiajie Lu, Jian Xiao, Weiyi Xia, Chongan Huang, Xiangyang Wang
Summary: The study demonstrates that 18 beta-GA has therapeutic effects on OA in DMM mouse model, suppressing inflammation and expression of degradative enzymes, reversing degradation of aggrecan and type II collagen. These findings suggest that 18 beta-GA could be a potential therapeutic agent for osteoarthritis.
Article
Cell Biology
Qihui Liu, Quanli Yang, Zengfeng Wu, Yanfang Chen, Miaomiao Xu, Hua Zhang, Jiliang Zhao, Zonghua Liu, Zerong Guan, Jing Luo, Zhi-yong Li, Guodong Sun, Qiong Wen, Yan Xu, Zhenhua Li, Kebing Chen, Xiaosong Ben, Wanchun He, Xueshi Li, Zhinan Yin, Jianlei Hao, Ligong Lu
Summary: This study reveals the accumulation of gamma delta T cells in fibrotic liver and their role in alleviating liver fibrosis. The activation of mTOR signaling in gamma delta T cells is observed during CCl4 treatment. IL-1 beta activation promotes the upregulation of CXCR3 expression through the mTORC2 signaling pathway in gamma delta T cells, leading to their migration into the liver and improvement of liver fibrosis.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Daniel Kucsera, Viktoria E. Toth, Nabil V. Sayour, Tamas Kovacs, Tamas G. Gergely, Mihaly Ruppert, Tamas Radovits, Alexandra Fabian, Attila Kovacs, Bela Merkely, Peter Ferdinandy, Zoltan V. Varga
Summary: This study aimed to investigate the hepatic and cardiac effects of an IL-1 beta targeting monoclonal antibody in an aged mouse model of NASH. The results showed that IL-1 beta inhibition improved cardiac diastolic function, but did not ameliorate features of NASH and may promote hepatic oncogenic transformation.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Dylan J. Sebo, Audrey R. Fetsko, Kallie K. Phipps, Michael R. Taylor
Summary: In this study, we identified the functional zebrafish Il1r1 using a genetic model of Il-1 beta-induced inflammation, providing valuable new insights for studying inflammatory conditions specifically driven by Il-1 beta.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dora Bencze, Tunde Fekete, Walter Pfliegler, Arpad Szoor, Eszter Csoma, Antonia Szanto, Tunde Tarr, Attila Bacsi, Lajos Kemeny, Zoltan Vereb, Kitti Pazmandi
Summary: The study reveals the presence of the NLRP3-dependent IL-1β secretory pathway in pDCs, which only prevails under non-dominant inflammatory conditions. The type I interferon pathway and IL-1β pathway interact with each other, with interferon inhibiting IL-1β production in pDCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Jiangnan Li, Jie Song, Li Kang, Li Huang, Shijun Zhou, Liang Hu, Jun Zheng, Changyao Li, Xianfeng Zhang, Xijun He, Dongming Zhao, Zhigao Bu, Changjiang Weng
Summary: The study revealed that ASFV infection inhibits the production of IL-1 beta and type I IFNs in porcine alveolar macrophages, highlighting the critical role of pMGF505-7R in this process. ASFV lacking the MGF505-7R gene showed reduced virulence in pigs and induced higher levels of IL-1 beta and IFN-beta production. The findings provide insights into the functions of ASFV-encoded pMGF505-7R and its impact on viral pathogenesis, potentially aiding in the development of antiviral strategies or vaccines to control ASF.
Article
Immunology
Julia E. Rood, Ayman Rezk, Jennifer Pogoriler, Laura S. Finn, Jon M. Burnham, Maureen B. Josephson, Amit Bar-Or, Edward M. Behrens, Scott W. Canna
Summary: This case report describes the improvement of a patient with refractory SJIA-LD after treatment with MAS-825, including pulmonary symptoms, lung inflammation, and burden of immunomodulatory therapy. This suggests that simultaneous targeting of both IL-1 beta and IL-18 may be a safe and effective treatment strategy in SJIA-LD.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Allergy
Philipp Starkl, Nicolas Gaudenzio, Thomas Marichal, Laurent L. Reber, Riccardo Sibilano, Martin L. Watzenboeck, Frederic Fontaine, Andre C. Mueller, Mindy Tsai, Sylvia Knapp, Stephen J. Galli
Summary: The study found that IgE sensitization enhances MC detoxification of honeybee venom by promoting proteolytic degradation and heparin-related interference with toxicity. This research emphasizes the importance of IgE, MCs, and specific MC products in defense against honeybee venom.
Article
Respiratory System
Martin L. Watzenboeck, Anna-Dorothea Gorki, Federica Quattrone, Riem Gawish, Stefan Schwarz, Christopher Lambers, Peter Jaksch, Karin Lakovits, Sophie Zahalka, Nina Rahimi, Philipp Starkl, Doerte Symmank, Tyler Artner, Celine Pattaroni, Nikolaus Fortelny, Kristaps Klavins, Florian Frommlet, Benjamin J. Marsland, Konrad Hoetzenecker, Stefanie Widder, Sylvia Knapp
Summary: Lung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases, but the mortality rate is high due to chronic lung allograft dysfunction (CLAD). The mechanisms leading to CLAD are not well understood due to insufficient understanding of post-transplant adaptation processes. This study analyzed bronchoalveolar lavage samples from lung recipients and donors, and found that recipient-specific and environmental factors shape the long-term lung microbiome. Certain bacterial strains were found to be correlated with underlying lung diseases even after transplantation. Machine learning techniques accurately predicted future changes in lung function, with the microbial profiles showing high predictive power. The study highlights the importance of understanding lung adaptation processes and the role of microbiome in predicting allograft function.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Anna-Dorothea Gorki, Dorte Symmank, Sophie Zahalka, Karin Lakovits, Anastasiya Hladik, Brigitte Langer, Barbara Maurer, Veronika Sexl, Renate Kain, Sylvia Knapp
Summary: This study proposes a novel culture model for studying and expanding murine primary alveolar macrophages (AMs) in vitro over several months. The cultured AMs maintain typical features and surface markers, and exhibit similar functions and transcriptional profile to primary AMs. When transferred into AM-deficient mice, the cultured AMs efficiently engraft in the lung and perform key macrophage functions.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Hematology
Katharina Woess, Sabine Macho-Maschler, Dorette S. van Ingen Schenau, Miriam Butler, Caroline Lassnig, Daniel Valcanover, Andrea Poelzl, Katrin Meissl, Barbara Maurer, Tania Brandstoetter, Claus Vogl, Anna Koren, Stefan Kubicek, Anna Orlova, Richard Moriggl, Birgit Strobl, Veronika Sexl, Frank N. van Leeuwen, Roland P. Kuiper, Mathias Muelle
Summary: TYK2 mutations can cause leukemia, and this study shows that TYK2 inhibitors combined with mTOR or CDK4/6 inhibitors can be a potential treatment for TYK2-driven acute leukemia.
Article
Virology
Thomas Demoulins, Marie-Laurence Baron, Dominique Gauchat, Nadia Kettaf, Steven James Reed, Tania Charpentier, Ulrich Kalinke, Alain Lamarre, Rafi Ahmed, Rafick-Pierre Sekaly, Surojit Sarkar, Vandana Kalia
Summary: This study found that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged effects in chronic infections compared to acute infections. The loss of thymic output was linked to inhibition of early stages of thymopoiesis and pronounced apoptosis during the late stages. Furthermore, the study revealed both direct and indirect effects of IFN-I on thymocytes, suggesting potential immunotherapeutic strategies targeting IFN-1 signals to manipulate disease outcomes in chronic infections and cancers.
Article
Biology
Riem Gawish, Philipp Starkl, Lisabeth Pimenov, Anastasiya Hladik, Karin Lakovits, Felicitas Oberndorfer, Shane J. F. Cronin, Anna Ohradanova-Repic, Gerald Wirnsberger, Benedikt Agerer, Lukas Endler, Tumay Capraz, Jan W. Perthold, Domagoj Cikes, Rubina Koglgruber, Astrid Hagelkruys, Nuria Montserrat, Ali Mirazimi, Louis Boon, Hannes Stockinger, Andreas Bergthaler, Chris Oostenbrink, Josef M. Penninger, Sylvia Knapp
Summary: Despite progress in understanding COVID-19, limited mechanistic insight into immunological factors and disease severity remains. Scientists generated a mouse-adapted SARS-CoV-2 strain, maVie16, and found that cytokine-driven immunopathology and ACE2 dependence determine disease severity. This study provides a new tool for discovering therapies.
Editorial Material
Biochemistry & Molecular Biology
Jennifer Becker, Ulrich Kalinke
Summary: This study investigated the relationship between pDC numbers, IFN-I serum levels, and disease severity in COVID-19 patients, and explored the molecular mechanisms underlying SARS-CoV-2-mediated pDC stimulation to induce cytokine responses.
Article
Biochemistry & Molecular Biology
Lukas Mathias Michaely, Lukas Schuwerk, Lisa Allnoch, Kathleen Schoen, Inken Waltl, Pia-Katharina Larsen, Andreas Pavlou, Chittappen Kandiyil Prajeeth, Guus F. Rimmelzwaan, Stefanie C. Becker, Ulrich Kalinke, Wolfgang Baumgaertner, Ingo Gerhauser
Summary: Rift Valley fever is an emerging disease with zoonotic characteristics. This study investigated the role of immune response in disease progression using an attenuated strain of RVFV. The results showed that IFNAR signaling can prevent systemic spread of the virus, but not its dissemination to the central nervous system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Nyamdelger Sukhbaatar, Maria Schoeller, Stephanie Deborah Fritsch, Monika Linke, Stefanie Horer, Manuela Traeger, Mario Mazic, Stephan Forisch, Karine Gonzales, Jan Pascal Kahler, Carina Binder, Caroline Lassnig, Birgit Strobl, Mathias Mueller, Barbara Scheiber-Mojdehkar, Claudia Gundacker, Stefanie Dabsch, Renate Kain, Markus Hengstschlaeger, Steven H. L. Verhelst, Guenter Weiss, Igor Theurl, Thomas Weichhart
Summary: Iron is a crucial cellular metal for various physiological functions. Its absorption from the diet and transport by transferrin is important for iron metabolism. Regulation of iron absorption and transfer remains poorly understood. In this study, macrophage-specific deletion of Tsc2, a negative regulator of mTORC1, in mice led to defects in iron metabolism, including impaired erythropoiesis and reduced Tf saturation. This was due to an iron import block in the duodenal epithelial cells. Activation of mTORC1 in duodenal macrophages promoted Tf degradation, while depletion of macrophages increased Tf levels. Inhibition of mTORC1 or serine protease activity restored Tf levels in the Tsc2-deficient mice. These findings suggest that duodenal macrophages regulate iron transfer by controlling Tf availability.
Article
Multidisciplinary Sciences
Martina Barends, Nicole Koller, Christian Schoelz, Veronica Duran, Berislav Bosnjak, Jennifer Becker, Marius Doering, Hanna Blees, Reinhold Foerster, Ulrich Kalinke, Robert Tampe
Summary: By studying human dendritic cells, we discovered that additional proteins are recruited to the peptide-loading complex (PLC) during dendritic cell differentiation and maturation, including BAP31, VAPA, and ESYT1. These proteins colocalize with TAP and are in close proximity to the PLC, indicating that the antigen processing machinery is located near ER exit- and membrane contact sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Sara Scinicariello, Adrian Soderholm, Markus Schaefer, Alexandra Shulkina, Irene Schwartz, Kathrin Hacker, Rebeca Gogova, Robert Kalis, Kimon Froussios, Valentina Budroni, Annika Bestehorn, Tim Clausen, Pavel Kovarik, Johannes Zuber, Gijs A. Versteeg
Summary: Tristetraprolin (TTP) stability is controlled by factors including lysine-ubiquitination and phosphorylation. The E3 ligase HUWE1 was identified as a regulator of TTP stability, indirectly controlling its phosphorylation. This study provides new insights into the regulation of TTP and its impact on immune response.
Article
Neurosciences
Lara-Jasmin Schroeder, Felix Mulenge, Andreas Pavlou, Thomas Skripuletz, Martin Stangel, Viktoria Gudi, Ulrich Kalinke
Summary: In this study, the researchers investigated the transcriptomic signatures of astrocytes during demyelination and remyelination in the cuprizone mouse model. They found that reactive astrocytes showed an inflammatory response during demyelination, while during remyelination, there was a shift towards tissue remodeling and regeneration. These findings highlight the dynamic nature of astrocyte functions during neurodegeneration and regeneration.
Article
Multidisciplinary Sciences
Ulrike Schmidt, Betuel Uluca, Iva Vokic, Barizah Malik, Thomas Kolbe, Caroline Lassnig, Martin Holcmann, Veronica Moreno-Viedma, Bernhard Robl, Carina Muehlberger, Dagmar Gotthardt, Maria Sibilia, Thomas Ruelicke, Mathias Mueller, Agnes Csiszar
Summary: FAM3C/ILEI is an important factor in epithelial-to-mesenchymal transition (EMT) induction, tumor progression, and metastasis. In this study, the researchers generated a new Tet-ON inducible Fam3c/ILEI transgenic mouse strain, providing a versatile tool to model the effect of elevated ILEI expression in various tissue entities and disease conditions, including cancer.
Article
Cell Biology
Kunjan Harit, Rituparna Bhattacharjee, Kai Matuschewski, Jennifer Becker, Ulrich Kalinke, Dirk Schlueter, Gopala Nishanth
Summary: This study reveals that the deubiquitinating enzyme OTUD7b prevents TNF-induced apoptosis of dendritic cells (DCs) during infection, resulting in efficient immune response. OTUD7b stabilizes the E3 ligase TNF-receptor-associated factor 2 (TRAF2) by counteracting its K48-ubiquitination, facilitating the activation of NF-κB and MAP kinases, IL-12 production, and expression of anti-apoptotic cFLIP and Bcl-xL. Mice with DC-specific OTUD7b-deficiency showed DC apoptosis and failure to induce CD8(+) T cell-mediated brain pathology in a murine malaria infection model. These findings highlight the importance of OTUD7b as a central molecular switch for DC survival and provide insights for manipulating DC responses.
CELL DEATH & DISEASE
(2023)