Article
Immunology
Elisa Toppi, Laura Sireno, Micaela Lembo, Nerisa Banaj, Beatrice Messina, Sedigheh Golesorkhtafti, Gianfranco Spalletta, Paola Bossu
Summary: Homotaurine is a potential therapeutic compound for Alzheimer's disease (AD) and has anti-inflammatory properties. This study suggests that supplementation of homotaurine in patients with mild cognitive impairment (MCI) increases the levels of anti-inflammatory cytokines IL-10 and IL-33, while decreasing the levels of pro-inflammatory cytokine IL-18. The elevation of IL-10 and IL-33 is associated with improved episodic memory in treated patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Leticia Gonzalez, Katherine Rivera, Marcelo E. Andia, Gonzalo Martinez Rodriguez
Summary: The IL-1 superfamily of cytokines, consisting of 11 cytokines and 10 receptors, is a crucial regulator of immunity and inflammation. It is tightly regulated through decoy receptor, receptor antagonists, and signaling inhibitors. Inflammation plays a central role in the development of atherosclerosis, and studies have shown the involvement of IL-1 cytokines and receptors in cardiovascular disease pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Aurelie Najm, Iain B. McInnes
Summary: IL-23, a pro-inflammatory cytokine secreted by dendritic cells and macrophages, plays a key role in the pathogenesis of rheumatic diseases by promoting T cell differentiation into Th17 cells. Therapeutic strategies targeting IL-23 have shown efficiency in PsA but not yet in RA.
Review
Immunology
Praxedis Martin, Jeremie D. Goldstein, Loic Mermoud, Alejandro Diaz-Barreiro, Gaby Palmer
Summary: IL-1 family cytokines play important roles in skin disorders, and dysregulated signaling may lead to the development of chronic inflammatory diseases. Anti-inflammatory IL-1 family members such as IL-1Ra and IL-36Ra control the biological activity of pro-inflammatory IL-1 family agonists. These cytokines are highly expressed in the epidermis and have therapeutic potential for human inflammatory skin diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Bhalchandra Mirlekar, Yuliya Pylayeva-Gupta
Summary: The IL-12 family cytokines are crucial in regulating tumor immune contexture and activating anti-tumor immune responses. Different family members have distinct roles, encompassing both promoting effector responses and inhibitory functions. These cytokines hold promise as candidates for developing immunomodulatory therapeutic approaches.
Article
Biology
Julie Y. Zhou, Carlos A. Alvarez, Brian A. Cobb
Summary: Cells integrate concurrent signaling initiated by different cytokines to produce specific responses, and the combinatorial effects of different cytokines can lead to distinct biological outcomes, understanding this signaling pathway is crucial for addressing diseases.
Article
Immunology
Yu-Hsiang Hsu, Chih-Hsing Wu, Chiao-Juno Chiu, Wei-Ting Chen, Yi-Chieh Chang, Martin Wabitsch, Ming-Shi Chang
Summary: IL-20 plays a critical role in obesity-induced inflammation and insulin resistance by regulating various pathways. It shows potential as a novel target for treating obesity and insulin resistance in patients with metabolic disorders.
Article
Dermatology
Laura Calabrese, Francesca Ney, Rui Aoki, Chiara Moltrasio, Angelo V. Marzano, Pia-Charlotte Stadler, Takashi K. Satoh, Lars E. French, Katrin Kerl
Summary: This study investigates the expression of cytokines in Sweet syndrome (SS) and finds that IL-1β, IL-36, and IL-1R3 are significantly overexpressed, suggesting their potential role in the pathogenesis of SS.
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Immunology
Nerissa T. Viola, James E. Glassbrook, Jhansi R. Kalluri, Justin B. Hackett, Madison N. Wicker, Joshua Sternberg, Heather M. Gibson
Summary: This study reports the development and evaluation of an antibody-based IL-12-specific PET tracer. The tracer showed the ability to accurately monitor IL-12 production and uptake in an animal model, providing a noninvasive method to study immune processes such as tumor immunity, inflammation, and infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Immunology
Cecilia Garlanda, Domenico Supino
Summary: The researchers in this study designed a new drug to selectively inhibit IL-1 by analyzing an IL-1 receptor missense mutation associated with un-leashed IL-1-mediated inflammation.
Article
Microbiology
Zane Vitenberga-Verza, Mara Pilmane, Ksenija Serstnova, Ivars Melderis, Lukasz Gontar, Maksymilian Kochanski, Andzelika Drutowska, Gergely Maroti, Beatriz Prieto-Simon
Summary: This study aimed to investigate the inflammatory and regulatory cytokines in the milk of dairy cows with subclinical and clinical mastitis. The results showed that IL-1 alpha, IL-4, and IL-17A drive the inflammatory responses in mastitis cases. Furthermore, the host defense response in mastitis is characterized by the continuation or resolution of the initial inflammation.
Article
Biology
Nathanael A. Caveney, Caleb R. Glassman, Kevin M. Jude, Naotaka Tsutsumi, K. Christopher Garcia
Summary: Interleukin 27 (IL-27) is a heterodimeric cytokine that plays an important role in immune homeostasis. This study used cryogenic-electron microscopy to determine the quaternary structure of IL-27 and its receptor complex, providing insights into the receptor assembly mechanism and distinguishing it from related cytokines.
Article
Cell Biology
Shima Makaremi, Ali Asgarzadeh, Hamed Kianfar, Alireza Mohammadnia, Vahid Asghariazar, Elham Safarzadeh
Summary: A global pandemic has emerged due to the novel coronavirus, causing widespread mortality worldwide. The immune response and cytokines play crucial roles in combating the virus, but excessive inflammation can contribute to severe COVID-19.
INFLAMMATION RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Seth D. Merkley, Samuel M. Goodfellow, Yan Guo, Zoe E. R. Wilton, Janie R. Byrum, Kurt C. Schwalm, Darrell L. Dinwiddie, Rama R. Gullapalli, Vojo Deretic, Anthony Jimenez Hernandez, Steven B. Bradfute, Julie G. In, Eliseo F. Castillo
Summary: Expression of Atg5 in intestinal myeloid cells prevents dysbiosis and excessive intestinal inflammation by limiting IL-12 production. Mice with a genetic deletion of Atg5 in myeloid cells showed severe intestinal inflammation characterized by increased IFN-gamma production. Exacerbated colitis was linked to excess IL-12 secretion from Atg5-deficient myeloid cells and gut dysbiosis. Restoration of the intestinal microbiota or genetic deletion of IL-12 attenuated the intestinal inflammation in Atg5-deficient mice.
JOURNAL OF CROHNS & COLITIS
(2022)
Review
Biochemistry & Molecular Biology
Ester Alves da Silva Amorim, Aquila Alcantara de Franca, Valeria Rego Alves Pereira, Maria Carolina Accioly Brelaz-de-Castro
Summary: The cytokines of the IL-1 family play a crucial role in initiating an effective immune response in Leishmania infection, primarily affecting the Th1 profile and potentially contributing to self-regulation of inflammation in Cutaneous Leishmaniasis. Studies in mice and humans have shed light on the role of these cytokines, emphasizing the importance of further research into them as potential new targets in the context of CL.
CYTOKINE & GROWTH FACTOR REVIEWS
(2021)
Article
Biochemical Research Methods
Erwin Pannecoucke, Laurens Raes, Savvas N. Savvides
Summary: The study found that the hematopoietic receptor FLT3 is activated by dimerization with a monomeric cytokine FL (FLL27D), rather than through receptor-receptor contacts.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Shubham Semwal, Rabah Boukherroub, Savvas N. Savvides, Julie Bouckaert
Summary: Glioblastoma is a deadly brain tumor with limited treatment options, requiring novel approaches to be explored. Immunoglobulin-M may play a significant role in glioblastoma and could potentially offer new treatment possibilities.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Review
Pharmacology & Pharmacy
Deepansh Mody, Julie Bouckaert, Savvas N. Savvides, Vibha Gupta
Summary: Research on the differential expression of HDAC isoforms in different types of breast cancer cells may lead to the discovery of selective HDAC inhibitors for personalized treatment.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Editorial Material
Biochemistry & Molecular Biology
Kenneth Verstraete, Koen H. G. Verschueren, Ann Dansercoer, Savvas N. Savvides
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Klaas Yperman, Anna C. Papageorgiou, Romain Merceron, Steven De Munck, Yehudi Bloch, Dominique Eeckhout, Qihang Jiang, Pieter Tack, Rosa Grigoryan, Thomas Evangelidis, Jelle Van Leene, Laszlo Vincze, Peter Vandenabeele, Frank Vanhaecke, Martin Potocky, Geert De Jaeger, Savvas N. Savvides, Konstantinos Tripsianes, Roman Pleskot, Daniel Van Damme
Summary: This study elucidated the structural and functional roles of the EH domains of the TPC subunit AtEH1/Pan1 in plant Clathrin-mediated endocytosis (CME). The research integrated high-resolution structural information obtained by X-ray crystallography and NMR spectroscopy with all-atom molecular dynamics simulations to provide insights into the function of both EH domains. The study revealed distinct but complementary roles of the EH domains of AtEH/Pan1 in plant CME and connected the internalization of SCAMP5 to the TPLATE complex.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Helena Aegerter, Ursula Smole, Ines Heyndrickx, Kenneth Verstraete, Savvas N. Savvides, Hamida Hammad, Bart N. Lambrecht
Summary: Protein crystals derived from innate immune cells have been associated with a Type-2 immune response for over 150 years in both mice and humans. These crystals, found in parasitic infections and diseases like asthma, can benefit the host during worm infections but also worsen inflammation and mucus production in asthma.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Steven Timmermans, Nicolette J. D. Verhoog, Kelly Van Looveren, Sylviane Dewaele, Tino Hochepied, Melanie Eggermont, Barbara Gilbert, Anne Boerema-de Munck, Tineke Vanderhaeghen, Joke Vanden Berghe, Natalia Garcia Gonzalez, Jolien Vandewalle, Yehudi Bloch, Mathias Provost, Savvas N. Savvides, Karolien De Bosscher, Wim Declercq, Robbert J. Rottier, Ann Louw, Claude Libert
Summary: The GR(dim/dim) mice with reduced dimerization propensity have helped define the functions of GR monomers and dimers, while the newly generated GR(D+L/D+L) mice exhibit insufficient ligand binding, leading to perinatal lethality.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Steven De Munck, Mathias Provost, Michiko Kurikawa, Ikuko Omori, Junko Mukohyama, Jan Felix, Yehudi Bloch, Omar Abdel-Wahab, J. Fernando Bazan, Akihide Yoshimi, Savvas N. Savvides
Summary: ALK and LTK are recently identified receptor tyrosine kinases involved in neural development, cancer, and autoimmune diseases, along with their activating cytokines ALKAL1 and ALKAL2. Structural studies reveal a unique architecture of the cytokine-binding segments, and propose a mechanistic blueprint for the complexes of ALK family receptors.
Article
Biochemistry & Molecular Biology
Sam Detry, Julie Andries, Yehudi Bloch, Cem Gabay, Danielle M. Clancy, Savvas N. Savvides
Summary: In this study, the sequestration mechanism of human IL-18 mediated by IL-18BP was elucidated based on the crystal structure of the IL-18:IL-18BP complex. The detailed structural analysis revealed the interaction landscape and ultra-high affinity of IL-18BP towards IL-18. The study also discovered a novel tetramer assembly, which effectively restrains IL-18 activity. These findings provide insights for structuredriven therapeutic strategies and further functional interrogation of IL-18.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Katarzyna Skladanowska, Yehudi Bloch, Jamie Strand, Kerry F. White, Jing Hua, Daniel Aldridge, Martin Welin, Derek T. Logan, Arne Soete, Romain Merceron, Casey Murphy, Mathias Provost, J. Fernando Bazan, Christopher A. Hunter, Jonathan A. Hill, Savvas N. Savvides
Summary: This study presents crystal structures of IL-27 and its receptor, providing insights into their interaction and offering a foundation for further research and therapeutic targeting of IL-27-related diseases.
Article
Ecology
Logan H. H. Hodgskiss, Michael Melcher, Melina Kerou, Weiqiang Chen, Rafael I. I. Ponce-Toledo, Savvas N. N. Savvides, Stefanie Wienkoop, Markus Hartl, Christa Schleper
Summary: Ammonia oxidation is a critical process in the global nitrogen cycle, but the fundamental knowledge of its key enzyme, the copper-dependent ammonia monooxygenase, is lacking for ammonia-oxidizing archaea (AOA). This study investigates the enzyme's structure in two AOA using blue-native gel electrophoresis and proteomics. Two new protein subunits, AmoY and AmoZ, unique to AOA, were identified, and their genes are linked to other AMO subunit genes in streamlined AOA genomes. These findings provide avenues for further understanding the structure and function of this ecologically important nitrification complex.
Review
Cell Biology
Peter Vandenabeele, Geert Bultynck, Savvas N. Savvides
Summary: Regulated cell death (RCD) relies on the activation and recruitment of pore-forming proteins (PFPs) to execute specific cell death pathways. This review discusses the structural rearrangements incurred by RCD-related PFPs and describes the mechanisms behind the conversion from an autoinhibited state to a membrane-embedded state. It also highlights the formation and maturation of membrane pores and the implications of different cell death modalities on physiological and pathophysiological processes.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Manoel Prouteau, Clelia Bourgoint, Jan Felix, Lenny Bonadei, Yashar Sadian, Caroline Gabus, Savvas N. Savvides, Irina Gutsche, Ambroise Desfosses, Robbie Loewith
Summary: Target of rapamycin complex 1 (TORC1) is a protein kinase that regulates cell homeostasis and growth in response to nutrients and stresses. This study found that glucose depletion in Saccharomyces cerevisiae triggers the formation of a large, inactive condensate called TOROID. The researchers demonstrated that the activity of the EGO complex (EGOC) controls the distribution of TOROID, independent of other nutrient-signaling pathways.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Correction
Ecology
Logan H. Hodgskiss, Michael Melcher, Melina Kerou, Weiqiang Chen, Rafael I. Ponce-Toledo, Savvas N. Savvides, Stefanie Wienkoop, Markus Hartl, Christa Schleper
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)