Article
Biochemistry & Molecular Biology
Justin Taft, Michael Markson, Diana Legarda, Roosheel Patel, Mark Chan, Louise Malle, Ashley Richardson, Conor Gruber, Marta Martin-Fernandez, Grazia M. S. Mancini, Jan A. M. van Laar, Philomine van Pelt, Sofija Buta, Beatrijs H. A. Wokke, Ira K. D. Sabli, Vanessa Sancho-Shimizu, Pallavi Pimpale Chavan, Oskar Schnappauf, Raju Khubchandani, Muserref Kasap Cuceoglu, Seza Ozen, Daniel L. Kastner, Adrian T. Ting, Ivona Aksentijevich, Iris H. I. M. Hollink, Dusan Bogunovic
Summary: The loss of TBK1 leads to decreased IFN-I induction but affects autoinflammation and TNF-induced cell death, and treatment with anti-TNF can improve the clinical condition of patients.
Article
Biochemistry & Molecular Biology
Shuang Zhang, Masayuki Harada, Takeshi Kimura, Noboru Ashida
Summary: Cancer-associated fibroblasts (CAFs) are important components of the tumor microenvironment and play critical roles in tumorigenesis. In this study, the researchers investigated the role of IKK beta, a key kinase for NF-kappa B activation, in activated CAFs. The results showed that IKK beta has a tumor-suppressing function in activated CAFs, and its deletion leads to enhanced tumor growth and upregulation of tumor-promoting factors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Kai Song, Xiaofeng Cai, Yunzhou Dong, Hao Wu, Yong Wei, Uma T. Shankavaram, Kui Cui, Yang Lee, Bo Zhu, Sudarshan Bhattacharjee, Beibei Wang, Kun Zhang, Aiyun Wen, Scott Wong, Lili Yu, Lijun Xia, Alana L. Welm, Diane R. Bielenberg, Kevin A. Camphausen, Yibin Kang, Hong Chen
Summary: ER-negative breast cancer exhibits elevated NF-kappa B activity, and here it is shown that epsin proteins play a pivotal role in promoting breast cancer by promoting NEMO linear ubiquitination and sustaining NF-kappa B signaling. The heightened levels of epsins in ER-negative breast cancer are associated with poor relapse-free survival, and targeting epsins may represent a strategy to restrain NF-kappa B signaling and provide a new perspective into ER-negative breast cancer treatment.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Pharmacology & Pharmacy
Christian Bailly
Summary: Amlexanox is a drug that has been used for decades to treat mouth aphthous ulcers and is now being considered for the treatment of diabetes and obesity. It has been found to have anticancer effects in various tumor models, and its efficacy can be enhanced when combined with other drugs. The drug has multiple protein targets and its molecular basis of action is discussed in this review. The use of Amlexanox as a cancer treatment should be further explored, and the development of new analogues is encouraged.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Zhu-Qi Huang, Wu Luo, Wei-Xin Li, Pan Chen, Zhe Wang, Rui-Jie Chen, Yi Wang, Wei-Jian Huang, Guang Liang
Summary: Costunolide (CTD) has anti-atherosclerotic effects by reducing inflammatory responses and oxLDL uptake, and its mechanism involves the inhibition of NF-kappa B signaling pathway through covalent binding to IKKβ.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Wei Xie, Qiwei Jiang, Xueji Wu, Lei Wang, Bing Gao, Zicheng Sun, Xiaomei Zhang, Lang Bu, Ying Lin, Qiang Huang, Jie Li, Jianping Guo
Summary: Research has revealed that IKBKE plays an oncogenic role in breast cancer metastasis by regulating the abundance of Snail. The findings suggest that targeting IKBKE could be a potential therapeutic strategy for metastatic breast cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Julia Busch, Rita Moreno, Laureano de la Vega, Vera Vivian Saul, Susanne Bacher, Felix von Zweydorf, Marius Ueffing, Axel Weber, Christian Johannes Gloeckner, Uwe Linne, Michael Kracht, Michael Lienhard Schmitz
Summary: Phosphorylation of TRAF6 by IKKε plays a crucial role in regulating its degradation, signaling networks and linking metabolic and inflammatory processes, which has implications for cancer research.
Letter
Biochemistry & Molecular Biology
Adnan Erol
Summary: Oxidative stress plays a significant role in the development of obesity-related nephropathy (ORN). A causal relationship between IKK and ORN via CYLD-mediated inhibition of NRF2 has been identified. However, contradictory explanations regarding the mechanisms involved need clarification.
MOLECULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Seoyun Yum, Minghao Li, Yan Fang, Zhijian J. Chen
Summary: This study shows that STING can function independently of type I interferons and autophagy, and that TBK1 recruitment to STING is essential for antiviral and antitumor immunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Eileen Dahlke, Toni Engmann, Yaman Anan, Robert Haesler, Giovanni Solinas, Franziska Theilig
Summary: Acute kidney injury (AKI) is a common renal injury with significant morbidity and mortality worldwide. This study investigated the role of NF-kappa B in AKI and found that its deletion improved renal function, reduced tissue damage and fibrosis, and enhanced vascularization, metabolism, reactive species disposal, and fine-tuned cell proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
John Victor Napoleon, Satish Sagar, Sydney P. Kubica, Lidia Boghean, Smit Kour, Hannah M. King, Yogesh A. Sonawane, Ayrianne J. Crawford, Nagsen Gautam, Smitha Kizhake, Pawel A. Bialk, Eric Kmiec, Jayapal Reddy Mallareddy, Prathamesh P. Patil, Sandeep Rana, Sarbjit Singh, Janani Prahlad, Paul M. Grandgenett, Gloria E. O. Borgstahl, Gargi Ghosal, Yazen Alnouti, Michael A. Hollingsworth, Prakash Radhakrishnan, Amarnath Natarajan
Summary: Activation of IKK beta, characterized by phosphorylation of serine residues 177 and 181, has been implicated in the early onset of cancer. This study used various models to assess the role of IKK beta and its activation in cancer, and identified 39-100 as a potent inhibitor of MAP3K1. It was found that IKK beta activation is critical for tumor growth in Kras mutant pancreatic cancer, and the compound 39-100 inhibits MAP3K1-mediated IKK beta phosphorylation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Aaron Seth Tooley, Dubek Kazyken, Cagri Bodur, Ian E. Gonzalez, Diane C. Fingar
Summary: TBK1 can directly activate mTOR complex 2 (mTORC2) to promote Akt phosphorylation, involving in cellular metabolism and proliferation. Interaction between TBK1 and mTOR serves as key nodes in two major signaling networks.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Fisheries
Baoyu Huang, Xiuxiu Sang, Juan Dong, Lingling Li, Xiaona Wang, Baoju Yang, Lei Wei, Yaqiong Liu, Meiwei Zhang, Xiaotong Wang
Summary: The TBK1/IKK epsilon gene in Pacific oysters plays a crucial role in immune signaling, response to pathogen infection, and regulation of NF-kappa B and ISRE reporter genes activation. It may act as a key signal transduction molecule and immune activity regulator in the oyster immune system.
Article
Medicine, General & Internal
Yumei Cao, Su'an Tang, Xiaoyu Nie, Zuoqing Zhou, Guangfeng Ruan, Weiyu Han, Zhaohua Zhu, Changhai Ding
Summary: The study identified miR-214-3p as a key regulator in osteoarthritis, impacting ECM metabolism and cell apoptosis in cartilage by modulating the NF-kappa B signaling pathway. Targeting IKKP, decreased miR-214-3p exacerbates OA development, suggesting it as a potential novel therapeutic target for OA.
Article
Cell Biology
Qianqian Huang, Sheng Chen, Xiaowei Xiong, Tingting Yin, Yanan Zhang, Guohua Zeng, Qiren Huang
Summary: Vascular endothelium dysfunction caused by endothelium inflammation is a trigger of numerous cardiovascular diseases. This study investigated the effect of Asprosin (ASP) on endothelium inflammation induced by hyperlipidemia. The results showed that ASP may play a pro-inflammation role in obesity-associated endothelium dysfunction, and could be a potential target for the prevention and treatment of obesity-related cardiovascular diseases.
Article
Oncology
Adele M. Nicolas, Marina Pesic, Esther Engel, Paul K. Ziegler, Markus Diefenhardt, Kilian B. Kennel, Florian Buettner, Claire Conche, Valentina Petrocelli, Eiman Elwakeel, Andreas Weigert, Anna Zinoveva, Maximilian Fleischmann, Bjoern Haeupl, Cem Karakuetuek, Hanibal Bohnenberger, Mohammed H. Mosa, Lars Kaderali, Jochen Gaedcke, Michael Ghadimi, Franz Roedel, Melek C. Arkan, Thomas Oellerich, Claus Roedel, Emmanouil Fokas, Florian R. Greten
Summary: The study reveals that inflammatory cancer-associated fibroblasts (iCAFs) in rectal cancer patients are associated with poor response to chemoradiotherapy. The researchers found that interleukin-1 alpha (IL-1 alpha) not only polarizes iCAFs towards an inflammatory phenotype but also triggers oxidative DNA damage, leading to p53-mediated therapy-induced senescence. This senescence of iCAFs results in chemoradiotherapy resistance and disease progression. Inhibition of IL-1 signaling or prevention of iCAFs senescence could sensitize mice to irradiation and improve therapy response.
Article
Dermatology
M. Otto, B. Dorn, T. Grasmik, M. Doll, M. Meissner, T. Jakob, I Hrgovic
Summary: Apremilast effectively inhibits pro-inflammatory responses in activated human umbilical vein endothelial cells, suggesting its therapeutic potential in preventing cardiovascular diseases in patients with chronic inflammatory conditions.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Multidisciplinary Sciences
Andreas Weigert, Xiang Zheng, Alina Nenzel, Kati Turkowski, Stefan Guenther, Elisabeth Strack, Evelyn Sirait-Fischer, Eiman Elwakeel, Ivan M. Kur, Vandana S. Nikam, Chanil Valasarajan, Hauke Winter, Alexander Wissgott, Robert Voswinkel, Friedrich Grimminger, Bernhard Brune, Werner Seeger, Soni Savai Pullamsetti, Rajkumar Savai
Summary: This study identifies the crucial role of fibrocytes in the progression and metastasis of lung cancer. Through experiments, it is demonstrated that fibrocytes can enhance the features of the cancer niche and promote cancer cell proliferation and migration. Lung cancer patients also exhibit an increased number of fibrocytes. The upregulation of endothelin and its receptors contributes to the interaction between fibrocytes and the cancer niche.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Xiang Zheng, Poonam Sarode, Andreas Weigert, Kati Turkowski, Prakash Chelladurai, Stefan Guenther, Carsten Kuenne, Hauke Winter, Albrecht Stenzinger, Simone Reu, Friedrich Grimminger, Thorsten Stiewe, Werner Seeger, Soni Savai Pullamsetti, Rajkumar Savai
Summary: Tumor-associated macrophages (TAMs), including antitumor M1-like TAMs and protumor M2-like TAMs, play diverse roles in lung cancer development. It has been found that the spatial proximity of HDAC2-overexpressing M2-like TAMs to tumor cells is significantly correlated with poor overall survival of lung cancer patients. Suppression of HDAC2 in TAMs alters macrophage phenotype, migration, and signaling pathways related to interleukins, chemokines, cytokines, and T-cell activation.
Article
Biochemistry & Molecular Biology
Arnaud Huard, Christian Wilmes, Anastasiia Kiprina, Christoph Netzer, Gaby Palmer, Bernhard Bruene, Andreas Weigert
Summary: IL-38 is an IL-1 family receptor antagonist that plays a role in chronic inflammatory diseases. It is expressed in epithelial cells as well as immune system cells, including macrophages and B cells. IL-38 affects B cell biology, with IL-38-deficient mice showing alterations in plasma cells and antibody levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Andreas Weigert, Lina Herhaus
Summary: Autophagy is a mechanism of cellular homeostasis that degrades cellular constituents, but it can also actively communicate with neighboring cells through a process called secretory autophagy. Secretory autophagy utilizes extracellular vesicles to secrete cellular content, which can modulate the functional profile of recipient cells. The immune system can sense these secreted molecules, including extracellular vesicles, and initiate the restoration of tissue homeostasis.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Florestan J. Koll, Severine Banek, Luis Kluth, Jens Koellermann, Katrin Bankov, Felix K. -H. Chun, Peter J. Wild, Andreas Weigert, Henning Reis
Summary: We analyzed the immune cells in the tumor microenvironment of 101 patients with muscle-invasive urothelial bladder cancer using multiplex immunohistochemistry. We found that high concentrations of macrophages were associated with increased risk of death, while high concentrations of Tregs were associated with decreased risk of death. We also identified two clusters, one with a high concentration of macrophages and the other with a high concentration of Tregs, which were associated with the worst and best survival rates, respectively.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Veronika Lutz, Veronique M. Hellmund, Felix S. R. Picard, Hartmann Raifer, Teresa Ruckenbrod, Matthias Klein, Tobias Bopp, Rajkumar Savai, Peter Duewell, Corinna U. Keber, Andreas Weigert, Ho-Ryun Chung, Malte Buchholz, Andre Menke, Thomas M. Gress, Magdalena Huber, Christian Bauer
Summary: Signaling through IL18R induces exhaustion of CD8(+) T cells, characterized by expression of coinhibitory receptors and loss of effector function. This exhaustion is mediated by an NLRP3-expressing tumor microenvironment that releases IL18. These findings suggest that NLRP3-mediated IL18R signaling could be a potential target for immunotherapy in pancreatic carcinoma.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Physiology
Timothy Warwick, Giulia Karolin Buchmann, Beatrice Pflueger-Mueller, Manuela Spaeth, Christoph Schuermann, Wesley Abplanalp, Lukas Tombor, David John, Andreas Weigert, Martin Leo-Hansmann, Stefanie Dimmeler, Ralf P. Brandes
Summary: Treatment of vascular stenosis with angioplasty can cause acute vascular damage, leading to restenosis. Single-cell RNA sequencing analysis of mouse carotid tissue after wire injury revealed the presence of smooth muscle cells that are also associated with atherosclerosis and myocardial infarction. These cells, called SEM cells, show specific gene expression patterns that could be targeted therapeutically to combat restenosis development.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Immunology
Maximilian Haist, Justus Kaufmann, Ivan-Maximiliano Kur, Stefanie Zimmer, Stephan Grabbe, Heinz Schmidberger, Andreas Weigert, Arnulf Mayer
Summary: In this study, the infiltration of CD8 T cells and the expression of PD-L1 were found to be significantly associated with the efficacy and survival of chemoradiotherapy in patients with oropharyngeal cancer. However, tumor cell proliferation and the expression of stem cell markers showed no independent prognostic effect.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Verena Wilmes, Ivan M. Kur, Andreas Weigert, Marcel A. Verhoff, Elise Gradhand, Silke Kauferstein
Summary: This study examines the expression of iNOS and NT production in postmortem human myocardial infarction hearts. The results demonstrate that resident macrophages are the main source of iNOS expression in these hearts, and there is a correlation between iNOS and NT production, indicating the involvement of iNOS in oxidative stress.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Annika Karger, Siavash Mansouri, Matthias S. Leisegang, Andreas Weigert, Stefan Guenther, Carsten Kuenne, Ilka Wittig, Sven Zukunft, Stephan Klatt, Blerina Aliraj, Laura Klotz, Hauke Winter, Poornima Mahavadi, Ingrid Fleming, Clemens Ruppert, Biruta Witte, Ibrahim Alkoudmani, Stefan Gattenloehner, Friedrich Grimminger, Werner Seeger, Soni Savai Pullamsetti, Rajkumar Savai
Summary: Long noncoding RNAs (lncRNAs) play a role in gene transcription in many cells, but their function in tumor-associated macrophages (TAMs) is not well understood. The lncRNA ADPGK-AS1 is upregulated in M2-like human macrophages, macrophages exposed to lung cancer cells, and TAMs from human lung cancer tissue. Overexpression of ADPGK-AS1 promotes an M2-like, tumor-promoting phenotype in macrophages, while its knockdown induces an M1-like, tumor-suppressive phenotype, inhibiting lung tumor growth.
Article
Cell Biology
Tobias F. Primke, Rebecca Ingelfinger, Mohammed A. F. Elewa, Igor Macinkovic, Andreas Weigert, Matthias P. Fabritius, Christoph A. Reichel, Angelika Ullrich, Uli Kazmaier, Luisa D. Burgers, Robert Fuerst
Summary: Research has found that depolymerizing microtubule-targeting agents can reduce inflammation by inhibiting the expression of pro-inflammatory molecules and decreasing leukocyte adhesion to endothelial cells. These agents not only affect leukocytes but also significantly decrease the inflammatory response of vascular endothelial cells. The study sets a baseline for further exploration of the anti-inflammatory effects of depolymerizing microtubule-targeting agents.
Meeting Abstract
Medicine, Research & Experimental
Florestan Koll, Jens Koellermann, Luis Kluth, Severine Banek, Felix Chun, Andreas Weigert, Peter Wild, Henning Reis
LABORATORY INVESTIGATION
(2023)
Article
Biology
Pauline Hog, Silvia Kuntschar, Peter Rappl, Arnaud Huard, Andreas Weigert, Bernhard Bruene, Tobias Schmid
Summary: Macrophages are a versatile immune cell group involved in inflammatory reactions. This study reveals that prostaglandin E-2 (PGE(2)) may contribute to the regulation of Lyve1 expression and impact inflammatory responses. PGE(2) synergizes with dexamethasone to enhance Lyve1 expression, while CD44 expression remains unchanged. Lyve1-expressing macrophages integrate inflammatory stimuli with extracellular matrix-derived signals.