Article
Biology
Veethika Pandey, Alicia Fleming-Martinez, Ligia Bastea, Heike R. Doeppler, Jillian Eisenhauer, Tam Le, Brandy Edenfield, Peter Storz
Summary: This study highlights the importance of CXCL10/CXCR3 signaling in the early phase of murine pancreatic cancer, demonstrating its role in mediating chemotaxis, proliferation, and maintenance of inflammatory identity in macrophages within the pancreas. Inhibition of CXCL10/CXCR3 signaling shifts macrophage populations to a tumor-promoting phenotype, increasing fibrosis and lesion progression.
Article
Immunology
Xuan Wang, Mara Lennard Richard, Tomika S. Caldwell, Kamala Sundararaj, Shuzo Sato, Tamara K. Nowling, Xian K. Zhang
Summary: The transcription factor Fli-1 is involved in the pathogenesis of lupus disease by regulating the expression of CXCL10 and CXCR3, which play important roles in renal inflammation and damage. Targeting Fli-1 or the CXCL10-CXCR3 axis may provide new approaches for lupus treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Peiyu Liang, Xinyi Zhang, Yahui Zhang, Yifan Wu, Yinghao Song, Xueyang Wang, Taoxiang Chen, Wanhong Liu, Biwen Peng, Jun Yin, Fanggang He, Yuanteng Fan, Song Han, Xiaohua He
Summary: Epilepsy is a common neurological disorder, and a new form of cell death called ferroptosis is associated with seizures. This study found that neuronal ferroptosis dependent on GPX4-GSH was detected in epileptic mice and could be attenuated by ferroptosis inhibitors. Additionally, neurotoxic A1 astrocytes activated in epilepsy facilitated seizure-related neuronal ferroptosis. Inhibiting ferroptosis blocked A1 astrocyte-induced neurotoxicity. A1 astrocyte-secreted CXCL10 enhanced STAT3 phosphorylation but suppressed SLC7A11 in neurons, leading to ferroptosis-associated lipid peroxidation in a GPX4-dependent manner. Clinical findings also showed a significant correlation between neuronal ferroptosis and A1 astrocytes in epileptic patients. In conclusion, this study reveals that A1 astrocyte-induced neuronal ferroptosis contributes to the pathogenesis of epilepsy, providing a novel therapeutic target for precision medicine.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Medicine, Research & Experimental
Yuki Sasaki, Hideki Arimochi, Kunihiro Otsuka, Hiroyuki Kondo, Shin-ichi Tsukumo, Koji Yasutomo
Summary: Immunoproteasome dysfunction leads to proteasome-associated autoinflammatory syndromes. In a mouse model, Psmb8 mutation causes hyperactivation of the CXCR3 pathway, resulting in increased susceptibility to skin inflammation.
Article
Cell Biology
Naureen Javeed, Tracy K. Her, Matthew R. Brown, Patrick Vanderboom, Kuntol Rakshit, Aoife M. Egan, Adrian Vella, Ian Lanza, Aleksey Matveyenko
Summary: The study demonstrates that pro-inflammatory beta cell-derived small EVs disrupt beta cell function, promote inflammatory responses, and enhance immune cell recruitment in the islets. Furthermore, CXCL10 chemokine enriched in these EVs binds to CXCR3 receptors on beta cells, modulating inflammatory gene expression and leukocyte recruitment.
Article
Microbiology
Ruonan Liang, Shuaiyin Chen, Yuefei Jin, Ling Tao, Wangquan Ji, Peiyu Zhu, Dong Li, Yu Zhang, Weiguo Zhang, Guangcai Duan
Summary: CVA2 infection leads to HFMD outbreaks, causing systemic inflammatory response and central nervous system inflammation. This study reveals the involvement of the CXCL10/CXCR3 axis in CVA2 immunopathogenesis, with activation of this axis contributing to apoptosis, proinflammatory cytokine expression, and inflammatory cell infiltration, which can be reversed by alpha CXCR3 therapy.
MICROBIOLOGY SPECTRUM
(2022)
Article
Neurosciences
Yan-Fang Kong, Wei-Lin Sha, Xiao-Bo Wu, Lin-Xia Zhao, Ling-Jie Ma, Yong-Jing Gao
Summary: Chemokines and their receptors play a role in chronic pain pathogenesis, with CXCR3 and CXCL10 specifically influencing neuronal excitability in the dorsal root ganglion. Activation of CXCR3 by CXCL10 leads to p38 and ERK activation in DRG neurons, enhancing neuronal excitability and contributing to neuropathic pain maintenance.
NEUROSCIENCE BULLETIN
(2021)
Article
Medicine, Research & Experimental
Jan-Hendrik Riedel, Lennart Robben, Hans-Joachim Paust, Yu Zhao, Nariaki Asada, Ning Song, Anett Peters, Anna Kaffke, Alina Borchers, Gisa Tiegs, Larissa Seifert, Nicola M. Tomas, Elion Hoxha, Ulrich O. Wenzel, Tobias B. Huber, Thorsten Wiech, Jan-Eric Turner, Christian F. Krebs, Ulf Panzer
Summary: Glucocorticoids, a cornerstone of therapy for autoimmune and chronic inflammatory diseases, exert their therapeutic effects by reducing the number of proinflammatory T cells in the kidney. This study found that high-dose steroid treatment decreases the recruitment of CXCR3(+)CD4(+) T cells to the inflamed kidneys by acting directly on renal tissue cells, leading to an amelioration of the disease course. The study identified the CXCL9/CXCL10-CXCR3 axis as a previously unrecognized cellular and molecular target of glucocorticoids.
Article
Plant Sciences
Qiuping Li, Jing Sun, Yuxue Cao, Baojun Liu, Zhengxiao Zhao, Lingli Hu, Hu Zhang, Qing Kong, Jinfeng Wu, Jingcheng Dong
Summary: This study aimed to investigate the effects of ICT on CD8+ T cell chemotaxis and the CXCL10/CXCR3 axis in an in vitro model of COPD. The results showed that ICT significantly suppressed the expression and secretion of key chemokines in macrophages, indirectly inhibiting CD8+ T cell chemotaxis. Additionally, ICT had no significant effect on CD8+ T cell proliferation or apoptosis, and the mechanism of action may involve downregulation of the TGF-beta-Smad2 signaling pathway.
Article
Immunology
Sho Hosaka, Kazuo Imagawa, Yusuke Yano, Lisheng Lin, Junko Shiono, Miho Takahashi-Igari, Hideki Hara, Daisuke Hayashi, Hironori Imai, Atsushi Morita, Hiroko Fukushima, Hidetoshi Takada
Summary: We found that the CXCL10-CXCR3 axis plays an important role in the pathogenesis of Kawasaki disease.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhengcheng Wang, Xiang Ao, Zhilin Shen, Luoquan Ao, Xiaofeng Wu, Chengxiu Pu, Wei Guo, Wei Xing, Min He, Hongfeng Yuan, Jianhua Yu, Ling Li, Xiang Xu
Summary: Chronic inflammation-induced metastases in cancer have been a significant obstacle in treatment. Recent studies have shown that TNF-alpha activates PI3K/Akt and p38 MAPK pathways to enhance CXCL10 transcription, promoting metastases in colon cancer cells. CXCL10, in turn, regulates EMT in colon cancer cells via the PI3K/Akt pathway, offering a new potential target for inhibiting colon cancer metastases.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Yunting Lin, Ruitao Lu, Jingmei Hou, Grace Guoying Zhou, Wenmin Fu
Summary: Radiotherapy is a common method for cancer treatment, but tumors may develop resistance to radiation due to the immune system. IFNgamma and CXCL10 play important roles in sensitizing tumor cells to ionizing radiation, and their interaction may contribute to effective killing of tumor cells in vitro.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Immunology
Shu Yin, Xin-yue Ma, Ying-feng Sun, Yan-qing Yin, Ying Long, Chun-lai Zhao, Jun-wei Ma, Sen Li, Yan Hu, Ming-tao Li, Gang Hu, Jia-wei Zhou
Summary: In this study, it was found that RGS5 promotes neurodegenerative processes by enhancing astrocytic TNFR signaling. RGS5 switches astrocytes from being neuroprotective to pro-inflammatory by interacting with TNFR2 and TNFR1. The transcription of astrocytic RGS5 is regulated by the transcription factor EBF-1. Blocking the astrocytic RGS5/TNFR interaction may be a potential therapeutic strategy for neuroinflammation-related neurodegenerative diseases.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Oncology
Yihe Yan, Leting Zheng, Qiang Du, Hamza Yazdani, Kun Dong, Yarong Guo, David A. Geller
Summary: IRF-1 regulates anti-tumor immunity in HCC by modulating CXCL10 and CXCR3, inhibiting proliferation and promoting apoptosis. It overcomes proliferation partly through activating the CXCL10/CXCR3 autocrine axis.
Review
Multidisciplinary Sciences
Gulistan Agirman, Kristie B. Yu, Elaine Y. Hsiao
Summary: The brain and gastrointestinal tract, as critical sensory organs, interact through immune cells along the gut-brain axis to regulate inflammatory responses and immune balance, affecting the physiological state of the body.
Review
Cell Biology
Sarah K. Deasy, Neta Erez
Summary: This review presents recent findings on how modifications of the extracellular matrix (ECM) support metastasis in common metastatic sites such as the lung, liver, bone, and brain. Shared ECM modifications as well as site-specific characteristics are discussed. Areas of technical innovation and further research are also explored.
TRENDS IN CELL BIOLOGY
(2022)
Review
Instruments & Instrumentation
Snezana Dordevic, Maria Medel Gonzalez, Inmaculada Conejos-Sanchez, Barbara Carreira, Sabina Pozzi, Rita C. Acurcio, Ronit Satchi-Fainaro, Helena F. Florindo, Maria J. Vicent
Summary: The field of nanomedicine faces challenges in regulatory clarity and consistency. Developing nanomedicines requires considerations of critical quality attributes, appropriate analytical methods, important process parameters, and pre-clinical models. Close collaboration with regulatory agencies is advised to accelerate the development of future nanomedicines.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Catia Monteiro, Lauritz Miarka, Maria Perea-Garcia, Neibla Priego, Pedro Garcia-Gomez, Laura Alvaro-Espinosa, Ana de Pablos-Aragoneses, Natalia Yebra, Diana Retana, Patricia Baena, Coral Fustero-Torre, Osvaldo Grana-Castro, Kevin Troule, Eduardo Caleiras, Patricia Tezanos, Pablo Muela, Elisa Cintado, Jose Luis Trejo, Juan Manuel Sepulveda, Pedro Gonzalez-Leon, Luis Jimenez-Roldan, Luis Miguel Moreno, Olga Esteban, Angel Perez-Nunez, Aurelio Hernandez-Lain, Jose Mazarico Gallego, Irene Ferrer, Rocio Suarez, Eva M. Garrido-Martin, Luis Paz-Ares, Celine Dalmasso, Elizabeth Cohen-Jonathan Moyal, Aurore Siegfried, Aisling Hegarty, Stephen Keelan, Damir Vareslija, Leonie S. Young, Malte Mohme, Yvonne Goy, Harriet Wikman, Jose Fernandez-Alen, Guillermo Blasco, Lucia Alcazar, Clara Cabanuz, Sergei Grivennikov, Andrada Ianus, Noam Shemesh, Claudia C. Faria, Rebecca Lee, Paul Lorigan, Emilie Le Rhun, Michael Weller, Riccardo Soffietti, Luca Bertero, Umberto Ricardi, Joaquim Bosch-Barrera, Elia Sais, Eduard Teixidor, Alejandro Hernandez-Martinez, Alfonso Calvo, Javier Aristu, Santiago M. Martin, Alvaro Gonzalez, Omer Adler, Neta Erez, Manuel Valiente
Summary: This study identifies a molecular mechanism underlying resistance to whole-brain radiotherapy and suggests potential targets and biomarkers for personalized radiotherapy. The findings have important implications for improving the efficacy of treatment for patients with brain metastasis.
Article
Biochemistry & Molecular Biology
Monica Argenziano, Irfan Aamer Ansari, Elisabetta Muntoni, Rita Spagnolo, Anna Scomparin, Roberta Cavalli
Summary: This study aims to improve the antioxidant activity and bioavailability of trans-resveratrol by developing lipid-coated nanocrystals. The nanocrystals obtained through a milling method showed faster dissolution rate compared to the coarse powder and did not impair the antioxidant properties of trans-resveratrol. Oral administration of the lipid-coated nanocrystals to rats resulted in increased bioavailability of trans-resveratrol.
Article
Multidisciplinary Sciences
Lea Monteran, Nour Ershaid, Hila Doron, Yael Zait, Ye'ela Scharff, Shahar Ben-Yosef, Camila Avivi, Iris Barshack, Amir Sonnenblick, Neta Erez
Summary: This study found that systemic treatment with doxorubicin following resection of triple-negative breast tumors induces the expression of complement factors in lung fibroblasts and modulates an immunosuppressive metastatic niche, thus promoting lung metastasis. Targeting complement signaling with pharmacological treatment can alleviate immune dysregulation and reduce lung metastasis.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Sabina Pozzi, Anna Scomparin, Dikla Ben-Shushan, Eilam Yeini, Paula Ofek, Alessio D. Nahmad, Shelly Soffer, Ariel Ionescu, Antonella Ruggiero, Adi Barzel, Henry Brem, Thomas M. Hyde, Iris Barshack, Sanju Sinha, Eytan Ruppin, Tomer Weiss, Asaf Madi, Eran Perlson, Inna Slutsky, Helena F. Florindo, Ronit Satchi-Fainaro
Summary: Resistance to chemo- and immunotherapies often develops in melanoma brain metastasis (MBM), with the brain microenvironment (BME) playing a role in promoting MBM progression. We found that monocyte chemoattractant protein-1 (MCP-1) and its receptors, CCR2 and CCR4, were overexpressed in MBM compared to primary lesions. We demonstrated that melanoma cells alter astrocyte secretome and induce MCP-1 expression and secretion, enhancing tumorigenic properties of melanoma cells. Pharmacological blockade of MCP-1 or molecular knockout of CCR2/CCR4 increased infiltration of cytotoxic CD8(+) T cells and attenuated the immunosuppressive phenotype of the BME, leading to decreased MBM growth and prolonged survival in mice.
Review
Pharmacology & Pharmacy
Chiara Puricelli, Casimiro Luca Gigliotti, Ian Stoppa, Sara Sacchetti, Deepika Pantham, Anna Scomparin, Roberta Rolla, Stefania Pizzimenti, Umberto Dianzani, Elena Boggio, Salvatore Sutti
Summary: Chronic inflammation plays a role in the development of various diseases, but conventional anti-inflammatory drugs are not very effective and have adverse effects. Encapsulating bioactive molecules in nanoparticles (NPs) may enhance their pharmacological properties. Poly lactic-co-glycolic acid (PLGA) NPs are widely used due to their compatibility, degradability, and ability to control erosion time, hydrophilicity, and mechanical properties. This review focuses on the use of PLGA NPs in preclinical in vivo models of diseases characterized by chronic inflammation or imbalanced inflammatory responses.
Article
Oncology
Omer Adler, Yael Zait, Noam Cohen, Raquel Blazquez, Hila Doron, Lea Monteran, Yeela Scharff, Tamar Shami, Dhanashree Mundhe, Gunther Glehr, Andrew A. Kanner, Suzana Horn, Vered Yahalom, Sebastian Haferkamp, James A. Hutchinson, Annalen Bleckmann, Limor Nahary, Itai Benhar, Shlomit Yust Katz, Tobias Pukrop, Neta Erez
Summary: Adler et al. have identified granulocyte-derived lipocalin-2 (LCN2) as a mediator of inflammatory astrocyte activation, which promotes brain metastasis in breast cancer and melanoma. Their findings highlight the importance of understanding the interactions between immune cells and astrocytes in the brain metastatic niche for developing better therapeutic strategies. LCN2 has been shown to induce neuroinflammation and its high levels in patient blood and brain metastases are strongly associated with disease progression and poor survival, making it a potential prognostic marker and therapeutic target.
Article
Oncology
Noam Cohen, Dhanashree Mundhe, Sarah K. Deasy, Omer Adler, Nour Ershaid, Tamar Shami, Oshrat Levi-Galibov, Rina Wassermann, Ruth Scherz-Shouval, Neta Erez
Summary: Metastatic cancer is difficult to cure and is the main cause of cancer-related deaths. In this study, the researchers found that cancer-associated fibroblasts play a crucial role in creating a favorable microenvironment for metastasis by mediating inflammation. They also discovered that a protein called Activin A is secreted from breast tumors and promotes fibrosis in the lung, which enhances metastasis. This new mechanism could potentially be targeted for therapeutic intervention to inhibit metastatic relapse.
Editorial Material
Oncology
Neta Erez
Summary: Mortality from cancer is mainly caused by tumor metastasis. Understanding the biology of tumor metastasis is a significant challenge in cancer research due to the incurable nature of advanced metastatic cancers. While the role of the microenvironment in facilitating tumor growth has been extensively studied, the involvement of the metastatic microenvironment in supporting the multistage process of metastasis remains largely unresolved. Investigating the intricate interactions between disseminated cancer cells and organ-specific microenvironments is essential for the development of effective therapeutic strategies to prevent metastatic relapse.
MOLECULAR ONCOLOGY
(2023)
Review
Oncology
Lena Neufeld, Eilam Yeini, Sabina Pozzi, Ronit Satchi-Fainaro
Summary: Three-dimensional bioprinted cancer models have the potential to revolutionize our understanding and treatment of cancer by revealing novel biomarkers and drug targets, advancing personalized cancer therapy, and replacing in vitro and animal models.
NATURE REVIEWS CANCER
(2022)
Review
Oncology
Dor Lavie, Aviad Ben-Shmuel, Neta Erez, Ruth Scherz-Shouval
Summary: Cancer-associated fibroblasts (CAFs) play a central role in the microenvironment of solid tumors, and recent advances in single-cell technologies have provided insights into their complexity and heterogeneity. Understanding the subsets and functions of CAFs can potentially lead to better therapeutic strategies for cancer.
