Article
Immunology
Joana Wilton, Filipa Lopes de Mendonca, Isabel Pereira-Castro, Michael Tellier, Takayuki Nojima, Angela M. Costa, Jaime Freitas, Shona Murphy, Maria Jose Oliveira, Nicholas J. Proudfoot, Alexandra Moreira
Summary: In this study, new 3'UTR-APA and IPA mRNA isoforms were found during pro-inflammatory polarization of primary human macrophages and CRC co-culture, which may be used as diagnostic or therapeutic tools in the future.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Virology
Julia Ettich, Julia Werner, Hendrik T. Weitz, Eva Mueller, Roland Schwarzer, Philipp A. Lang, Juergen Scheller, Jens M. Moll
Summary: This study has developed a novel dual-specificity inhibitor that can simultaneously target SARS-CoV-2 infection and virus-induced hyperinflammation. By fusing an inhibitor of viral cell entry with a molecule blocking IL-6, this molecule may have the potential to efficiently ameliorate symptoms of COVID-19 in infected individuals.
JOURNAL OF VIROLOGY
(2022)
Article
Psychiatry
Ting Sun, Qian Chen, Junchi Mei, Yan Li
Summary: This study found that the IL-6/sIL-6R/sgp130 complex was closely related to E2 levels in female patients with MDD. IL-6 and sgp130 may be valuable serum biomarkers for the diagnosis and prognosis of MDD in women.
Article
Cell Biology
Wei Feng, Panpan Yang, Hongrui Liu, Fan Zhang, Minqi Li
Summary: The combination of IL-6 and sIL-6R enhances the formation and bone resorption of osteoclasts induced by low levels of RANKL. Blocking sIL-6R can inhibit NF-kappa B and JNK signaling pathways to eliminate this promotive effect.
JOURNAL OF MOLECULAR HISTOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rossella Salemi, Giuseppe Gattuso, Barbara Tomasello, Alessandro Lavoro, Agostino Gaudio, Massimo Libra, Salvatore Santo Signorelli, Saverio Candido
Summary: This study investigated the involvement of IL-6 trans-signaling in DVT and found a strong correlation between the Asp358Ala variant and sIL6-R levels. The high frequency of the Asp358Ala mutation and elevated IL-6 levels in DVT patients may explain the association between IL-6 overactivation and DVT outcome. These findings provide a proof of concept for targeting IL-6 trans-signaling as a new strategy for DVT adjuvant therapy.
Review
Immunology
Stefan Rose-John, Brendan J. Jenkins, Christoph Garbers, Jens M. Moll, Juergen Scheller
Summary: This review discusses the discovery of the IL-6 trans-signalling pathway and the development of biologics that specifically inhibit this pathway. Targeting IL-6 trans-signalling can decrease disease-promoting activities of IL-6 without blocking its protective actions.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stefan Rose-John
Summary: IL-6 is a cytokine involved in immunity, neural cell maintenance, and metabolism. It is synthesized by various cells and its levels are elevated during infection and inflammation. IL-6 binds to a receptor complex and can also act on cells without the IL-6 receptor through trans-signaling.
Article
Nutrition & Dietetics
Saida Breuer, Philipp Kasper, Christina Vohlen, Ruth Janoschek, Thorben Hoffmann, Sarah Appel, Elena Mueller-Limberger, Andrea Mesaros, Stefan Rose-John, Christoph Garbers, Stefan Mueller, Jan-Wilm Lackmann, Esther Mahabir, Joerg Doetsch, Eva Hucklenbruch-Rother, Inga Bae-Gartz
Summary: Maternal obesity affects offspring's body weight and epigonadal white adipose tissue metabolism, predominantly independent of IL-6tS inhibition as shown in a transgenic mouse model. This highlights the importance of maternal and newborn nutrition for long-term offspring health.
Article
Biochemistry & Molecular Biology
Xiaohan Luan, Wenxian Yang, Xiaoyuan Bai, Heqiao Li, Huizi Li, Wenhui Fan, He Zhang, Wenjun Liu, Lei Sun
Summary: CypA positively regulates the IL-6 trans-signaling pathway by inhibiting degradation of IL-6 membrane receptor gp130 and enhancing its dimerization, while its expression is negatively regulated by SOCS1. SOCS1 interacts with CypA and promotes its degradation through ubiquitination, thus inhibiting the IL-6 trans-signaling pathway.
Article
Immunology
Anil K. Singh, Mahamudul Haque, Bhanupriya Madarampalli, Yuanyuan Shi, Benjamin J. Wildman, Abdul Basit, Sadik A. Khuder, Bhagwat Prasad, Quamarul Hassan, Salahuddin Ahmed, Madhu M. Ouseph
Summary: IL-6 trans-signaling induces molecular reprogramming of RASFs to osteoclast-like cells through the activation of transcription factor Ets2, leading to increased expression of osteoclast-specific proteins and markers of invasive phenotype.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Marc Jonathan George, Nur Hayati Jasmin, Valerie Taylor Cummings, Angela Richard-Loendt, Francesca Launchbury, Kevin Woollard, Tabitha Turner-Stokes, Ana Isabel Garcia Diaz, Mark Lythgoe, Daniel James Stuckey, Aroon Dinesh Hingorani, Derek William Gilroy
Summary: Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI), with the novel recombinant fusion protein sgp130Fc showing efficacy in exclusive trans-signaling blockade. In a rat model, sgp130Fc attenuated infiltration and preserved cardiac function, in contrast to anti-IL-6 antibodies that result in panantagonism.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Lena Marie Westermann, Anke Baranowsky, Giorgia Di Lorenzo, Tatyana Danyukova, Jamie Soul, Jean-Marc Schwartz, Gretl Hendrickx, Michael Amling, Stefan Rose-John, Christoph Garbers, Thorsten Schinke, Sandra Pohl
Summary: In a study on mice models, it was found that pharmacological blockade of IL-6 trans-signaling cannot correct the low bone mass phenotype in patients with mucolipidosis type II (MLII).
SCIENTIFIC REPORTS
(2021)
Article
Reproductive Biology
Sai-Jiao Li, Hsun-Ming Chang, Jiamin Xie, Jeremy H. Wang, Jing Yang, Peter C. K. Leung
Summary: This study elucidates the molecular mechanisms by which interleukin 6 trans-signaling upregulates the expression of prostaglandin-endoperoxide 2 and increases prostaglandin E-2 production in the human ovary.
BIOLOGY OF REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
Kun Ma, Jingluan Han, Zixu Zhang, Heying Li, Yanchang Zhao, Qinlong Zhu, Yongyao Xie, Yao-Guang Liu, Letian Chen
Summary: N-6-methyladenosine (m(6)A)) modification plays a crucial role in post-transcriptional regulation of eukaryotic gene expression, with OsEDM2L identified as a key protein essential for rice anther development through regulating the m(6)A modification of EAT1 mRNA to impact tapetal programmed cell death.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2021)
Article
Oncology
Zhiwu Jiang, Rui Liao, Jiang Lv, Shanglin Li, Diwei Zheng, Le Qin, Di Wu, Suimin Chen, Youguo Long, Qiting Wu, Suna Wang, Simiao Lin, Xiaohan Huang, Zhaoyang Tang, Pengcheng Shi, Hongsheng Zhou, Qifa Liu, Ruocong Zhao, Yangqiu Li, Yang Jie, Wei Wei, Peilong Lai, Xin Du, Shuzhong Cui, Robert Weinkove, Pentao Liu, Duanqing Pei, Yao Yao, Peng Li
Summary: CAR-T cell therapies have shown high clinical response rates in B cell malignancies, with potential for solid tumor treatment. Modulating IL-6 trans-signaling through GP130/STAT3 pathway enhances CAR-T cell expansion and antitumor activity, while GP130 expression in CAR-T cells improves antitumor efficacy without systemic IL-6 trans-signaling, indicating the potential for therapeutic applications.
Article
Chemistry, Multidisciplinary
Andreas Reif, Kevin Lam, Sascha Weidler, Marie Lott, Irene Boos, Juliane Lokau, Christian Bretscher, Manuel Moennich, Lukas Perkams, Marina Schmaelzlein, Christopher Graf, Jan-Patrick Fischer, Carolin Lechner, Kerstin Hallstein, Stefan Becker, Michael Weyand, Clemens Steegborn, Gerhard Schultheiss, Stefan Rose-John, Christoph Garbers, Carlo Unverzagt
Summary: A library of glycoforms of human interleukin 6 (IL-6) was generated using semisynthesis, and their in vivo plasma clearance rates in rats were evaluated. The results showed that IL-6 glycoforms with different structures exhibited varying clearance rates in the body, with 2,6-sialylated glycoforms of IL-6 being cleared faster in most cases.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Stefan Dusterhoft, Selcan Kahveci-Tuerkoez, Justyna Wozniak, Anke Seifert, Petr Kasparek, Henrike Ohm, Shixin Liu, Jana Kopkanova, Juliane Lokau, Christoph Garbers, Christian Preisinger, Radislav Sedlacek, Matthew Freeman, Andreas Ludwig
Summary: This study provides insights into the structure and function of the conserved iRhom homology domain (IRHD) and identifies a key motif within IRHD that affects the transport and stability of the iRhom-ADAM17 complex. Mutation of this motif hinders the secretion pathway and prolongs the half-life of iRhom2 and ADAM17. Additionally, disruption of this motif alters the interaction profile of iRhom2 with proteins involved in intracellular vesicle transport.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Birte Kespohl, Tim Schumertl, Jessica Bertrand, Juliane Lokau, Christoph Garbers
Summary: Bone development requires the coordinated action of different signaling pathways and cell types, with IL-11 playing a crucial regulatory role. Missense mutations in the IL11RA gene encoding IL-11R have been linked to craniosynostosis.
CYTOKINE & GROWTH FACTOR REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Elizabeta Georgieva, Stefan L. Leber, Cora Wex, Christoph Garbers
Summary: The study reveals that perturbation of the actin cytoskeleton is not sufficient to induce NF-kappa B activation and IL-6 secretion, but it reduces IL-6-induced activation of STAT3 in Hep3B cells. Additionally, IL-6 receptor proteolysis by ADAM10 is not dependent on the integrity of the actin cytoskeleton.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Yvonne J. Rosenberg, Xiaoming Jiang, Tracy Cheever, Felicity J. Coulter, Shilpi Pandey, Markus Sack, Lingjun Mao, Lori Urban, Jonathan Lees, Miranda Fischer, Jeremy Smedley, Heather Sidener, Jeffrey Stanton, Nancy L. Haigwood
Summary: Plant-produced antibodies showed promising results as passive immunoprophylaxis in a breastfeeding model in newborns. The use of human neutralizing antibodies effectively prevented infection in newborn monkeys and offered advantages in cost of production and safety. The findings suggest that anti-Env antibodies may play a role in controlling viral replication in this newborn model.
JOURNAL OF VIROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Juliane Lokau, Birte Kespohl, Sophia Kirschke, Christoph Garbers
Summary: IL-11, a member of the IL-6 family of cytokines, was originally discovered as a factor that promotes megakaryocyte maturation, but recent research has revealed its crucial roles in inflammation, fibrosis, and cancer. IL-11 initiates signaling through both classic and trans-signaling mechanisms, impacting the activation of cells that do not express the IL-11 receptor.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Tim Schumertl, Juliane Lokau, Stefan Rose-John, Christoph Garbers
Summary: Interleukin-6 (IL-6) is a pleiotropic cytokine involved in various physiological and pathophysiological functions. It can signal through different pathways, with trans-signaling playing a crucial role in its pro-inflammatory properties. The soluble form of the IL-6 receptor (sIL-6R) is generated by different mechanisms, including proteolysis. Attempts to selectively block IL-6 trans-signaling are being made in pre-clinical animal models and clinical studies for inflammatory bowel disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Anna Krone, Yan Fu, Simon Schreiber, Johanna Kotrba, Loisa Borde, Aileen Noetzold, Christoph Thurm, Jonas Negele, Tobias Franz, Sabine Stegemann-Koniszewski, Jens Schreiber, Christoph Garbers, Aniruddh Shukla, Robert Geffers, Burkhart Schraven, Dirk Reinhold, Anne Dudeck, Annegret Reinhold, Andreas J. Muller, Sascha Kahlfuss
Summary: Zinc aspartate (UNIZINK) negatively regulates gene networks and metabolism of CD4(+) T cells, leading to impaired function and viability. High doses of zinc prevent Th1 CNS autoimmunity and Th2 allergy.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Rabea Victoria Niehues, Justyna Wozniak, Florian Wiersch, Eva Lilienthal, Nikola Tacken, Tim Schumertl, Christoph Garbers, Andreas Ludwig, Stefan Duesterhoeft
Summary: This study shows that ADAM10 is an important shedding protease for ACE2, and ACE2 can also be released in extracellular vesicles. The degree of ACE2 shedding mediated by ADAM10 and ADAM17 depends on stimulatory conditions and the expression level of the ADAM17 regulator iRhom2.
Article
Biochemistry & Molecular Biology
Sophia Kirschke, Ireti Ogunsulire, Balachandar Selvakumar, Neele Schumacher, Tanya Sezin, Stefan Rose-John, Alexander Scheffold, Christoph Garbers, Juliane Lokau
Summary: The cytokine IL-2 plays a crucial role in immune homeostasis. This study demonstrates that metalloproteases ADAM10 and ADAM17 can cleave the IL-2R alpha, generating a soluble ectodomain that inhibits IL-2 signaling in T cells. Manipulating the cleavage of IL-2R alpha offers a potential opportunity to alter IL-2 function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Maria Angeles Rodriguez-Hernandez, David Carneros, Maria Nunez-Nunez, Ramon Coca, Rosario Baena, Gema M. Lopez-Ruiz, Maria Elena Cano-Serrano, Alberto Martinez-Telleria, Ana Fuentes-Lopez, Juan Manuel Praena-Fernandez, Christoph Garbers, Jose Hernandez-Quero, Federico Garcia, Stefan Rose-John, Matilde Bustos
Summary: IL-6 signaling variables serve as useful tools for early identification and stratification of COVID-19 patients, with significant implications for treatment and clinical decision-making.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Dominik M. Schulte, Georg H. Waetzig, Harald Schuett, Marlies Marx, Berenice Schulte, Christoph Garbers, Juliane Lokau, Ann-Kathrin Vlacil, Juliane Schulz, Anna K. Seoudy, Bernhard Schieffer, Philip Rosenstiel, Marcus Seeger, Matthias Laudes, Stefan Rose-John, Ulf Luetzen, Karsten Grote, Stefan Schreiber
Summary: Inflammation plays an important role in atherosclerotic cardiovascular disease, and there is a need for therapies targeting excessive inflammation. A fusion protein called olamkicept has been shown to reduce atherosclerosis independently of LDL cholesterol metabolism in mice, and its use in a patient with high-risk ASCVD also demonstrated a reduction in arterial wall inflammation.
FRONTIERS IN PHARMACOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Birte Kespohl, Roland Hartig, Yvonne Garbers, Juliane Lokau, Christoph Garbers
Article
Biochemistry & Molecular Biology
Birte Kespohl, Anna-Lena Hegele, Stefan Duesterhoeft, Hans Bakker, Falk F. R. Buettner, Roland Hartig, Juliane Lokau, Christoph Garbers
Summary: This study analyzed two variants of the interleukin-11 receptor (IL-11R) found in patients with craniosynostosis. The results showed that the IL-11R-E364_V368del variant is biologically active and processed normally, while the IL-11R-T306_S308dup variant is retained within the cell and unable to perform signal transduction.
Article
Hematology
Conny K. Baldauf, Peter Muller, Tobias R. Haage, Stephanie Adam-Frey, Juliane Lokau, Christoph Garbers, Thomas Fischer
Summary: The study found that anti-IL-6 treatment significantly reduced levels of certain inflammatory cytokines in serum, but did not improve hematological disease parameters in JAK2+/V617F mice or alleviate splenomegaly and spleen histopathology.
