Article
Biochemistry & Molecular Biology
Javier Estevez, Vicente Martinez
Summary: Toll-like receptors (TLRs) play a role in microbial regulation of gastrointestinal functions, including the epithelial barrier function (EBF). This study investigated the effects of TLR7 stimulation on colonic EBF in rats. Results showed that TLR7 stimulation with imiquimod had a pro-barrier effect, while the combination with dimethyl sulfoxide (DMSO) had a detrimental effect on EBF. These effects were not associated with changes in gene expression or distribution of tight junction-related proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Yuwei Zhang, Yang Li, Tong Mu, Nanwei Tong, Ping Cheng
Summary: The study demonstrated that utilizing VitA-coupled cationic liposomes delivered TLR4 shRNA more efficiently to aHSCs compared to uncoupled cationic liposomes, both in vitro and in vivo conditions. TLR4 gene silencing inhibited HSCs activation and alleviated liver fibrosis through NF-kappa B transcriptional inactivation, pro-inflammatory cytokines secretion, and ROS synthesis.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Chemistry, Medicinal
Ratna Kumar Sreekantha, Christopher P. Mussari, Dharmpal S. Dodd, Laxman Pasunoori, Subramanya Hegde, Shana L. Posy, David Critton, Stefan Ruepp, Murali Subramanian, Luisa M. Salter-Cid, Debarati Mazumder Tagore, Sanket Sarodaya, Shailesh Dudhgaonkar, Michael A. Poss, Gary L. Schieven, Percy H. Carter, John E. Macor, Alaric J. Dyckman
Summary: Toll-like receptors are crucial for activation of the innate immune system. Aberrant activation of TLR7 and TLR8 can lead to autoimmune disorders, and inhibition of their signaling holds promise for disease treatment. A study identified potent dual inhibitors of TLR7 and TLR8, which selectively targeted these receptors and showed promising in vitro and in vivo results.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Medicine, Research & Experimental
Valentina Salvi, Hoang Oanh Nguyen, Francesca Sozio, Tiziana Schioppa, Carolina Gaudenzi, Mattia Laffranchi, Patrizia Scapini, Mauro Passari, Ilaria Barbazza, Laura Tiberio, Nicola Tamassia, Cecilia Garlanda, Annalisa Del Prete, Marco A. Cassatella, Alberto Mantovani, Silvano Sozzani, Daniela Bosisio
Summary: The inflammatory and IFN pathways of innate immunity are crucial in the resistance and pathogenesis of COVID-19. Single-stranded RNA fragments from the SARS-CoV-2 genome were identified as direct activators of endosomal TLR7/8 and MyD88 pathway, inducing human DC activation and inflammatory responses. The virus endosomal processing products can potentiate IFN and inflammatory responses, playing a key role in host resistance and COVID-19 pathogenesis.
Article
Immunology
Chiung-Ya Chen, Yun-Fen Hung, Ching-Yen Tsai, Yi-Chun Shih, Ting-Fang Chou, Ming-Zong Lai, Ting-Fang Wang, Yi-Ping Hsueh
Summary: This study reveals the differential impacts of TLR3 and TLR7 signaling pathways on transcriptomic profiles in bone marrow-derived macrophages. Activation of TLR3 enhances innate immunity globally, while TLR7 signaling disrupts downstream signaling leading to the expression of cytokines and chemokines. Overall, TLR3 and TLR7 display different properties and provide useful mouse models for further investigation of these RNA-sensing TLRs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Melika Shafeghat, Sina Kazemian, Arya Aminorroaya, Zahra Aryan, Nima Rezaei
Summary: TLR-7 plays a crucial role in the pathogenesis and development of cardiovascular diseases by activating inflammatory responses and affecting the risk of thrombus formation. It has a two-sided effect, both increasing and decreasing the risk of cardiovascular problems.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Ryan Urak, Brenna Gittins, Citradewi Soemardy, Nicole Grepo, Lior Goldberg, Madeleine Maker, Galina Shevchenko, Alicia Davis, Shirley Li, Tristan Scott, Kevin V. Morris, Stephen J. Forman, Xiuli Wang
Summary: In this study, the impact of different shRNA elements on the knockdown efficiency of target genes in CAR T cells was evaluated. The results emphasize the importance of considering multiple shRNAs and their orientation for effective knockdown. It was also shown that using a strong promoter and avoiding self-targeting can enhance CAR T cell functionality. These findings provide a framework for the rational design of CAR T cells with shRNA-mediated knockdown capabilities, which can improve the therapeutic efficacy of CAR T cell-based immunotherapy.
Article
Medicine, Research & Experimental
Haylee A. Cosgrove, Sebastien Gingras, Minjung Kim, Sheldon Bastacky, Jeremy S. Tilstra, Mark J. Shlomchik
Summary: The regulatory role of Toll-like receptor 7 (TLR7) in the pathogenesis of lupus and its potential therapeutic strategy have been studied. The study found that TLR7 deficiency in B cells greatly improved the disease progression in TLR9-deficient mice with accelerated systemic lupus erythematosus, suggesting the importance of B cell-directed TLR7 regulation in lupus.
Article
Dermatology
Kyung-Ah Cho, Da-Won Choi, Minhwa Park, Yu-Hee Kim, So-Youn Woo
Summary: Stimulation of TLR7 leads to increased intracellular structures in mast cells and upregulation of genes involved in pro-inflammatory responses, suggesting a potential therapeutic target for IgE-independent skin inflammation.
ANNALS OF DERMATOLOGY
(2021)
Article
Hematology
Martina Fejtkova, Martina Sukova, Katerina Hlozkova, Karolina Skvarova Kramarzova, Marketa Rackova, David Jakubec, Marina Bakardjieva, Marketa Bloomfield, Adam Klocperk, Zuzana Parackova, Anna Sediva, Jahnavi Aluri, Michaela Novakova, Tomas Kalina, Eva Fronkova, Ondrej Hrusak, Hana Malcova, Petr Sedlacek, Zuzana Liba, Martin Kudr, Jan Stary, Megan A. Cooper, Michael Svaton, Veronika Kanderova
Summary: Our study identified a novel mutation c.1715G>T (p.G572V) in the Toll-like receptor 8 (TLR8) gene, which causes an autoimmune and autoinflammatory disorder in a family with monozygotic male twins. In vitro assays confirmed the pathogenicity of the mutation and revealed increased inflammatory responses.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Review
Cell Biology
Archittapon Nokkeaw, Pannathon Thamjamrassri, Pisit Tangkijvanich, Chaiyaboot Ariyachet
Summary: Chronic liver injury leads to HSC activation and production of excessive ECM, resulting in tissue fibrosis. Understanding the molecular mechanisms that control HSC activation could lead to the development of new anti-fibrotic therapies. Recent studies have identified circRNAs as new regulators in HSC activation, which can modulate miRNA activity involved in fibrogenic signaling cascades.
Article
Cell Biology
Yana Geng, Junyu Wang, Sandra Alejandra Serna-Salas, Alejandra Hernandez Villanueva, Manon Buist-Homan, Marco Arrese, Peter Olinga, Hans Blokzijl, Han Moshage
Summary: Liver fibrosis is a response of the liver to chronic inflammation. Hepatic stellate cells (HSCs) can induce the inflammatory phenotype in liver macrophages (KCs) through the release of extracellular vesicles (EVs), thereby promoting fibrosis. This effect is mediated by the activation of Toll-like receptor 4 (TLR4) signaling pathway.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Immunology
Thomas Wallach, Martin Raden, Lukas Hinkelmann, Mariam Brehm, Dominik Rabsch, Hannah Weidling, Christina Krueger, Helmut Kettenmann, Rolf Backofen, Seija Lehnardt
Summary: The COVID-19 pandemic, caused by SARS-CoV-2, leads to thromboembolic events and an inflammatory response in the body, including the brain. Machine learning was used to identify RNA fragments derived from the SARS-CoV-2 genome that can activate immune receptors TLR7 and TLR8. Experimental validation confirmed the activation of TLR7 and TLR8 by these RNA fragments, leading to cytokine release and inflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Chenglong Cheng, Yajie Wu, Xin Wang, Qiuyun Xue, Yurong Huang, Faxue Liao, Xiao Wang, Qiangjun Duan, Chenggui Miao
Summary: RNA methylation, especially m6A methylation, plays a crucial role in the occurrence and development of hepatic fibrosis (HF). The pathophysiological regulation of HF by RNA methylation is achieved through the interaction of methyltransferases, demethylases, and reading proteins, which may provide a new therapeutic and diagnostic target.
CELL AND BIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Bo-Kyeong Jung, Young Jun Kim, JinWoo Hong, Han-Gyu Chang, A-Rum Yoon, Chae-Ok Yun
Summary: Cancer is a complex and deadly disease with limited treatment options. Targeted therapy using small interfering RNA (siRNA) to silence cancer-enriched proteins is a powerful tool, but its application is limited. Oncolytic adenovirus-mediated therapy offers an alternative approach. This study reports the development of two oncolytic adenovirus systems that effectively and persistently target ErbB3.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)