Article
Chemistry, Multidisciplinary
Lanlan Li, Yongchang Ma, Yi Hu, Pengfei Wang, Songling Han, Xiangjun Zhang, Jianxiang Zhang
Summary: This article reports a targeted treatment method for asthma using a cyclic oligosaccharide-derived nanotherapy. The treatment effectively alleviates oxidative stress, suppresses inflammatory responses, reverses airway remodelling, and improves pulmonary function. The method shows promising results for the treatment of eosinophilic and neutrophilic asthma.
Article
Agriculture, Dairy & Animal Science
Wenxiang Shen, Ayodele Olaolu Oladejo, Xiaoyu Ma, Wei Jiang, Juanshan Zheng, Bereket Habte Imam, Shengyi Wang, Xiaohu Wu, Xuezhi Ding, Baohua Ma, Zuoting Yan
Summary: This study found that Cl-amidine effectively alleviated the inflammatory response to LPS-induced endometritis in rats by inhibiting the formation of NETs. Therefore, Cl-amidine could be a potential candidate for the treatment of endometritis.
Article
Biochemistry & Molecular Biology
Gustavo Silva-Oliveira, Leandra Linhares-Lacerda, Thayana R. F. Mattos, Camila Sanches, Tatiana Coelho-Sampaio, Ingo Riederer, Elvira M. Saraiva
Summary: Neutrophils release neutrophil extracellular traps (NETs) when they interact with different laminin (LM) isoforms. The induction of NETs by laminins is partially inhibited by anti-alpha 6 integrin antibody and requires elastase and peptidylarginine deiminase (PAD)-4. Laminins also enhance the release of NETs triggered by a protozoan parasite and exhibit leishmanicidal activity.
Editorial Material
Oncology
Phei Er Saw, Jianing Chen, Erwei Song
Summary: Neutrophil extracellular traps (NETs) are involved in both infection control and tumor metastasis. The study by Mousset et al. published in Cancer Cell reveals that chemotherapy-induced inflammation promotes NETosis in malignant tumors, leading to chemoresistance. This finding highlights the potential of targeting inflammatory NETs for cancer treatment.
Article
Immunology
Jeffrey R. Strich, Marcos J. Ramos-Benitez, Davide Randazzo, Sydney R. Stein, Ashley Babyak, Richard T. Davey, Anthony F. Suffredini, Richard W. Childs, Daniel S. Chertow
Summary: Neutrophil extracellular traps (NETs) play a role in immunothrombosis and mortality in COVID-19. The study demonstrates that R406 can inhibit NETs release and possibly mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Mengmeng Zhao, Zihui Zheng, Zheng Yin, Jishou Zhang, Shanshan Peng, Jianfang Liu, Wei Pan, Cheng Wei, Yao Xu, Juan-Juan Qin, Jun Wan, Menglong Wang
Summary: Recent studies have shown that neutrophils play a key role in the progression of heart failure, and Developmental Endothelial Locus-1 (DEL-1), an anti-inflammatory glycoprotein, has been found to have protective effects in various cardiovascular diseases. However, the specific role of DEL-1 in chronic heart failure is still unclear. This study used a mouse model of pressure overload-induced non-ischemic cardiac failure and found that DEL-1 deficiency worsened cardiac dysfunction and remodeling by promoting neutrophil infiltration and the formation of neutrophil extracellular traps (NETs) through the regulation of P38 signaling. In vitro experiments also showed that DEL-1 can inhibit P38 signaling and NETs formation in mouse neutrophils in a MAC-1-dependent manner.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Alessandra Romano, Nunziatina Laura Parrinello, Martina Barchitta, Rosy Manuele, Fabrizio Puglisi, Andrea Maugeri, Alessandro Barbato, Anna Maria Triolo, Cesarina Giallongo, Daniele Tibullo, Lucia La Ferla, Ciro Botta, Sergio Siragusa, Carmelo Iacobello, Arturo Montineri, Giovanni Li Volti, Antonella Agodi, Giuseppe Alberto Palumbo, Francesco Di Raimondo
Summary: By assessing NET-osis, we can gain insights into the immune response of COVID-19 patients and predict clinical patterns, disease severity, and viral clearance.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
Shanshan Huang, Yaohui Wang, Shibo Lin, Wei Guan, Hui Liang, Jiajia Shen
Summary: Neutrophil autophagy plays a crucial role in the formation of NETs and degradation of inflammatory factors in gouty arthritis. The study found that MSU crystals can induce the formation of NETs and activate neutrophil autophagy. Autophagy-related proteins, ATG7 and p53, work together to promote PAD4 expression and induce the formation of NETs. Regulating autophagy and interfering with the formation of NETs may be a potential therapeutic approach for gouty arthritis.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Rheumatology
Ji Hye Jeong, Su Jin Choi, Soo Min Ahn, Ji Seon Oh, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo, Seokchan Hong
Summary: This study found that synovial fluid macrophages can clear MSU crystal-induced NETs, and the proportion of CD14(+) macrophages is significantly inversely correlated with levels of MPO-dsDNA complex in the synovial fluid of gout patients. Additionally, synovial fluid CD14(+) macrophages cultured with NETs did not show a significant induction in pro- and anti-inflammatory cytokines.
ARTHRITIS RESEARCH & THERAPY
(2021)
Article
Cardiac & Cardiovascular Systems
Paolo Carai, Laura Florit Gonzalez, Stijn Van Bruggen, Valerie Spalart, Daria De Giorgio, Nadeche Geuens, Kimberly Martinod, Elizabeth Anne Vincent Jones, Stephane Heymans
Summary: The study investigates the contribution of neutrophils to the progression of viral myocarditis (VM) and found that inhibiting neutrophils and neutrophil extracellular traps (NETs) in the acute phase of VM can reduce cardiac inflammation and improve the pathological phenotype.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Minoru Inoue, Masahiro Enomoto, Michio Yoshimura, Takashi Mizowaki
Summary: The study shows that inhibition of Na+/Ca2+ exchange by EIPA and MIA can trigger NETotic cell death in neutrophils, indicating a new mechanism of infection-independent NET generation.
Article
Biochemistry & Molecular Biology
Matthias Kubler, Sebastian Beck, Silvia Fischer, Philipp Goetz, Konda Kumaraswami, Hellen Ishikawa-Ankerhold, Manuel Lasch, Elisabeth Deindl
Summary: The study shows that the absence of CIRP can improve angiogenesis and regeneration of ischemic muscle tissue, likely by influencing macrophage polarization towards regenerative M2-like macrophages.
Article
Biochemistry & Molecular Biology
Michio Okamoto, Rei Mizuno, Kenji Kawada, Yoshiro Itatani, Yoshiyuki Kiyasu, Keita Hanada, Wataru Hirata, Yasuyo Nishikawa, Hideyuki Masui, Naoko Sugimoto, Takuya Tamura, Susumu Inamoto, Yoshiharu Sakai, Kazutaka Obama
Summary: This study investigated the expression and clinical relevance of neutrophil extracellular traps (NETs) in colorectal cancers (CRCs). The results showed that high expression of intratumoral or systemic NETs correlated with poor relapse-free survival (RFS) in CRC patients. In vitro and in vivo experiments demonstrated that NETs promoted CRC cell migration mediated by neutrophil elastase (NE), and NE inhibition suppressed liver metastases in CRC cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Zhengze Lu, Yang Long, Jiaxin Li, Kebai Ren, Wei Zhao, Xuhui Wang, Chunyu Xia, Yashi Wang, Man Li, Zhirong Zhang, Qin He
Summary: The developed LA/DOX NP can inhibit inflammatory cell recruitment in the liver and lungs through multiple mechanisms, block NF-kappa B and STAT3 signaling pathways, thereby shutting down inflammatory feed-forward loops, providing a new therapeutic strategy for breast cancer and its metastasis.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Multidisciplinary Sciences
Hannes A. Baukmann, Justin L. Cope, Colin Bannard, Alexander R. E. C. Schwinges, Margaretha R. J. Lamparter, Sarah Groves, Charles N. J. Ravarani, Borko Amulic, Joern E. Klinger, Marco F. Schmidt
Summary: Despite the availability of vaccines to prevent SARS-CoV-2 infection, treating critically ill COVID-19 patients remains crucial. This study presents an alternative method for identifying drug repurposing targets by screening disease-causing traits, leading to the discovery of potential treatment targets for critical illness.
Review
Immunology
Daniela F. Quail, Borko Amulic, Monowar Aziz, Betsy J. Barnes, Evgeniy Eruslanov, Zvi G. Fridlender, Helen S. Goodridge, Zvi Granot, Andres Hidalgo, Anna Huttenlocher, Mariana J. Kaplan, Ilaria Malanchi, Taha Merghoub, Etienne Meylan, Vivek Mittal, Mikael J. Pittet, Andrea Rubio-Ponce, Irina A. Udalova, Timo K. van den Berg, Denisa D. Wagner, Ping Wang, Arturo Zychlinsky, Karin E. de Visser, Mikala Egeblad, Paul Kubes
Summary: This article discusses the functional states and heterogeneity of neutrophils in cancer and provides a consensus statement on the controversies and solutions in neutrophil research. Further research is needed to understand the role of neutrophils in cancer and explore potential novel opportunities for cancer treatment.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Chuyi Tan, Bridgette Reilly, Alok Jha, Atsushi Murao, Yongchan Lee, Max Brenner, Monowar Aziz, Ping Wang
Summary: This study suggests that eCIRP is actively released from viable macrophages through GSDMD pores. Inhibition of GSDMD can reduce the release of eCIRP and potentially inhibit eCIRP-mediated inflammation in sepsis.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Surgery
Sara Siskind, William Royster, Max Brenner, Ping Wang
Summary: Inhibiting the extracellular cold-inducible RNA-binding protein/triggering receptor expressed on myeloid cells-1 pathway with M3 attenuates acute kidney injury, indicating that M3 could be a potential therapeutic agent for treating acute kidney injury.
Article
Biochemistry & Molecular Biology
Satoshi Takizawa, Yongchan Lee, Asha Jacob, Monowar Aziz, Ping Wang
Summary: This study found that eCIRP induces trogocytosis of neutrophils during inflammation, and the trogocytosed neutrophils exhibit an exaggerated pro-inflammatory phenotype.
MOLECULAR MEDICINE
(2022)
Article
Immunology
Kensuke Murata, Atsushi Murao, Monowar Aziz, Ping Wang
Summary: Neutrophil heterogeneity in sepsis is a significant factor, and the extracellular cold-inducible RNA-binding protein (eCIRP) regulates neutrophil phenotype and function through TLR4. This study found that eCIRP can induce CD112 expression in neutrophils, promoting Th1 differentiation in sepsis.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Cassie Shu Zhu, Xiaoling Qiang, Weiqiang Chen, Jianhua Li, Xiqian Lan, Huan Yang, Jonathan Gong, Lance Becker, Ping Wang, Kevin J. Tracey, Haichao Wang
Summary: The expression and secretion of procathepsin-L (pCTS-L) induced by serum amyloid A (SAA) contributes to its late and systemic accumulation in sepsis. Inhibition of pCTS-L interaction may be a potential antibody-based strategy to prevent dysregulated immune responses mediated by late-acting cytokines.
Article
Neurosciences
Archna Sharma, Ezgi Sari, Yongchan Lee, Shivani Patel, Max Brenner, Philippe Marambaud, Ping Wang
Summary: Abnormal calcium homeostasis, activation of protease calpain, generation of p25 and hyperactivation of cyclin-dependent kinase 5 (Cdk5) have been implicated in neurogenerative diseases. The current study investigates how eCIRP regulates the signaling pathways involved in calcium and calpain, and uncovers a novel mechanism involving Ca2+ release from ER stores in an IL-6R alpha/PLC/IP3-dependent manner.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Surgery
Molly Kobritz, Colleen Nofi, Maria Sfakianos, Gene Coppa, Monowar Aziz, Ping Wang
Summary: H151 has the potential to therapeutically reduce acute intestinal injury in sepsis.
Article
Medicine, Research & Experimental
Hui Jin, Monowar Aziz, Atsushi Murao, Molly Kobritz, Andrew J. Shih, Robert P. Adelson, Max Brenner, Ping Wang
Summary: Extracellular cold-inducible RNA-binding protein (eCIRP) is a key factor in the severity and mortality of sepsis, which induces the formation of antigen-presenting aged neutrophils (APANs) through CD4+ T cell activation, Th1 polarization, and IFN-gamma-mediated hyper-NETosis. APANs exacerbate acute lung injury (ALI) and worsen the survival of septic animals. These findings highlight the role of eCIRP and APANs in sepsis pathogenesis and potential therapeutic targets.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Physiology
Zhijian Hu, Fangming Zhang, Max Brenner, Asha Jacob, Ping Wang
Summary: Renal ischemia-reperfusion (RIR)-induced acute kidney injury (AKI) is a common renal disorder with high morbidity and mortality. STING is a signaling pathway that mediates inflammation and injury through cytosolic DNA activation. eCIRP, a damage-associated molecular pattern, activates STING and worsens hemorrhagic shock. H151, a small molecule, inhibits eCIRP-induced STING activation in vitro and protects against RIR-induced AKI.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Timothy Borjas, Asha Jacob, Molly Kobritz, Gaifeng Ma, Chuyi Tan, Vihas Patel, Gene F. F. Coppa, Monowar Aziz, Ping Wang
Summary: This study investigates the potential of a synthetic miRNA called PS-OMe miR130 in inhibiting eCIRP-mediated inflammation and acute lung injury in sepsis. The results show that PS-OMe miR130 has a strong binding affinity to eCIRP, decreases inflammatory proteins, and improves survival in a murine model of sepsis. This synthetic miRNA, with enhanced stability and protection from nuclease activity, holds promise as a novel therapeutic approach.
MOLECULAR MEDICINE
(2023)
Article
Immunology
Mian Zhou, Monowar Aziz, Hao-Ting Yen, Gaifeng Ma, Atsushi Murao, Ping Wang
Summary: In this study, we identified a novel mechanism by which eCIRP impairs macrophage bacterial phagocytosis in sepsis. Increased eCIRP levels were associated with decreased bacterial clearance in infected mice. eCIRP inhibited actin remodeling in macrophages through the formation of a STAT3-beta PIX complex, resulting in phagocytic dysfunction. Inhibition of STAT3 rescued the macrophage phagocytic dysfunction induced by eCIRP.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)