David Shahnazaryan, Rana Khalil, Claire Wynne, Caroline A Jefferies, Joan Ní Gabhann-Dromgoole, Conor C Murphy
Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV-1) infection, is the commonest cause of infectious blindness in the developed world. Following infection the virus is initially suspended in the tear film, where it encounters a multi-pronged immune response comprising enzymes, complement, immunoglobulins and crucially, a range of anti-viral and pro-inflammatory cytokines. However, given that HSV-1 can overcome innate immune responses to establish lifelong latency throughout a susceptible individual's lifetime, there is significant interest in understanding the mechanisms employed by HSV-1 to downregulate the anti-viral type I interferon (IFN) mediated immune responses...
December 17, 2020: Scientific Reports
Meng-Shi Yang, Xiao-Jian Xu, Bin Zhang, Fei Niu, Bai-Yun Liu
The heterogeneity of traumatic brain injury (TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients. Targeting common processes across species may be an innovative strategy to combat debilitating TBI. In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact...
July 2021: Neural Regeneration Research
Ying Wu, Yongcan Zhou, Zhenjie Cao, Xiaojuan Chen, HeHe Du, Yun Sun
Vibrio harveyi is regarded as serious pathogen for marine fishes. However, host defense mechanisms involved in V. harveyi infection remain incompletely defined. The transcription factor IFN regulatory factor 7 (IRF7) is largely associated with host defense against viral infections, and the role of IRF7 during V. harveyi infection in fish has not been well illuminated previously. In this study, IRF7 from golden pompano (Trachinotus ovatus) was characterized (TroIRF7). The TroIRF7 gene is 1323 bp, which encodes 440 amino acid residues...
December 11, 2020: Developmental and Comparative Immunology
Biswas Neupane, Dhiraj Acharya, Farzana Nazneen, Gabriel Gonzalez-Fernandez, Alex Sutton Flynt, Fengwei Bai
Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-α2 expression thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient ( Il17a-/- ) mice expressed a higher level of IFN-α2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, which was also recapitulated in IL-17A receptor-deficient ( Il17ra-/- ) mice...
2020: Frontiers in Immunology
Ewa Leszczyńska, Edyta Makuch, Małgorzata Mitkiewicz, Izabella Jasyk, Miwako Narita, Sabina Górska, Tomasz Lipiński, Jakub Siednienko
Activation of TLR7 by small imidazoquinoline molecules such as R848 or R837 initiates signaling cascades leading to the activation of transcription factors, such as AP-1, NF-κB, and interferon regulatory factors (IRFs) and afterward to the induction of cytokines and anti-viral Type I IFNs. In general, TLRs mediate these effects by utilizing different intracellular signaling molecules, one of them is Mal. Mal is a protein closely related to the antibacterial response, and its role in the TLR7 pathways remains poorly understood...
November 25, 2020: International Journal of Molecular Sciences
Ying-Ying Chen, Yu-Feng Liu, Yong-Dong Liu, Xiao-Hui Deng, Jie Zhou
Hematopoietic stem cells (HSCs) maintain quiescence under steady state, however, they are compelled to proliferate and expand to replenish the blood system under stress. The molecular basis underlying stress hematopoiesis remains to be fully understood. In this study, we reported that IRF7 represents an important regulator of stress hematopoiesis. Interferon regulatory factor 7 (IRF7) was dispensable for normal hematopoiesis, whereas its deficiency significantly enhanced hematopoietic stem and progenitor cells (HSPCs) regeneration and improved long-term repopulation of HSCs under stress...
November 30, 2020: Stem Cells
Tao Li, Yiping Song, Xiuyu Bao, Jianqin Zhang
An increasing amount of evidence has revealed that microRNAs (miRNAs) participated in immune regulation and reaction to acute cold and heat stresses. As a new type of post-transcriptional regulatory factor, miRNA has received widespread attention; However, the specific mechanism used for this regulation still needs to be determined. In this study, thirty broilers at the same growth period were divided into three groups and treated with different temperature and humidity of CS (10-15 °C and 90% Relative Humidity (RH)), HS (39 °C and 90% RH), and NS (26 °C and 50-60% RH) respectively...
November 20, 2020: Animals: An Open Access Journal From MDPI
Yaoyao Zhu, Shijuan Shan, Huaping Zhao, Rongrong Liu, Hui Wang, Xinping Chen, Guiwen Yang, Hua Li
BACKGROUND: Interferon (IFN) regulatory factors (IRFs), as transcriptional regulatory factors, play important roles in regulating the expression of type I IFN and IFN- stimulated genes (ISGs) in innate immune responses. In addition, they participate in cell growth and development and regulate oncogenesis. RESULTS: In the present study, the cDNA sequence of IRF10 in common carp (Cyprinus carpio L.) was characterized (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52...
November 19, 2020: BMC Veterinary Research
Gabriele Greve, Julia Schüler, Björn A Grüning, Bettina Berberich, Julia Stomper, Dennis Zimmer, Lea Gutenkunst, Ulrike Bönisch, Ruth Meier, Nadja Blagitko-Dorfs, Olga Grishina, Dietmar Pfeifer, Dieter Weichenhan, Christoph Plass, Michael Lübbert
Hypomethylating agents (HMA) have become the backbone of non-intensive AML/MDS treatment, primarily by virtue of their activity in patients with adverse genetics, e.g., monosomal karyotypes, often with losses on chromosome 7, 5 or 17. However, no comparable activity is observed with cytarabine (AraC), a cytidine analogue without DNA-hypomethylating properties. As evidence exists for compounding hypermethylation and gene silencing of hemizygous tumor suppressor genes (TSG), we thus hypothesized that this effect may preferentially be reversed by the HMA decitabine (DAC) and azacitidine (AZA)...
November 17, 2020: Cancer Research
Yongli Guo, Zhifeng Song, Chenfeng Li, Yueyang Yu, Haiyue Dai, Xiuxin Luo, Yujiao Wang, Junwei Wang, Mingchun Gao
Interferon-chi (IFN-χ) is a type of function-unknown IFN. IFN-χ in bovines (BoIFN-χ) has evolved as a multigene family. This family comprises four IFN-χ subtypes, two of which are functional genes, which we demonstrated to (i) have antiviral and antiproliferative activities, (ii) be highly sensitive to trypsin, and (iii) remain stable with changes in pH and temperature. BoIFN-χ is a key intermediate in antiviral response, PAbs against BoIFN-χs could downregulate the transcriptional activation of ISGs induced by poly(I:C), and BoIFN-χs could be induced upon virus infection at the early and late phase...
2020: Frontiers in Immunology
Yuan Tan, Faqin Tang
Although novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated pulmonary inflammation has recently attracted great attention, its pathology and pathogenesis are not clear. Notably, due to both its high infective and pathogenicity, SARS-CoV-2 infection may cause a severe sometimes fatal respiratory disease. A specific vaccine, which relies on the analysis of SARS-CoV-2 structural protein-derived antigenic peptides, is indispensable for restraining the spread and reducing the mortality of SARS-CoV-2...
November 13, 2020: Medicinal Research Reviews
Jingyu Wang, Lang Gong, Weidong Zhang, Wanli Chen, Haoming Pan, Yuchen Zeng, Xingling Liang, Jun Ma, Guihong Zhang, Heng Wang
The Wnt/β-catenin signaling pathway is an evolutionarily highly conserved signaling pathway related to the replication of various viruses. However, the interaction between the Wnt/β-catenin pathway and porcine reproductive and respiratory syndrome virus (PRRSV) is unknown. In the present study, we showed that PRRSV-infected Marc-145 and PAM cells expressed high levels of c-myc and cyclinD1 mRNA and accumulation of β-catenin in the nucleus. PRRSV nonstructural proteins (Nsps) 1α, 1β, 3, 4, 7, 10, and 12, and proteins encoded by open reading frames (ORFs) 2b, 3, and 5 induced the activation of the Wnt pathway according to TOP/FOP luciferase reporter assay...
October 23, 2020: Veterinary Microbiology
Yan Deng, Sheng-Lan Guo, Jia-Quan Li, Shan-Shan Xie, Ying-Chuan Zhou, Bin Wei, Qian Wang, Fen Wang
BACKGROUND: Interferon regulatory factor 7 (IRF7) plays a key role to regulate an inflammatory response, inhibits vascular smooth cell proliferation and promotes apoptosis. But its role in pulmonary hypertension (PH) pathology is essentially unknown. We hypothesized that downregulation IRF7 promotes pulmonary vascular remodeling and that overexpression of IRF7 could slow the progression of PH. METHODS: mRNA, and protein levels of IRF7 were assessed in the lung samples and isolated pulmonary artery smooth muscle cells (PASMCs) from MCT-induced PH in rats...
November 2, 2020: Life Sciences
Ao Hu, Xiaobing Chen, Qunjie Bi, Yang Xiang, Rongrong Jin, Hua Ai, Yu Nie
Polarization regulation of tumor-association macrophages (TAMs) is a promising treatment method for tumors, but aiming at TAMs alone shows unsatisfactory therapeutic efficiency. Therefore, we designed a parallel and cascade control system for both macrophage polarization and tumor cell inhibition. The system is composed of cationic lipopeptides with an arginine-rich periphery (RLS) and anionic magnetic nanoparticles (MNPs) for fleet transfection of miR-125b. Based on the highly efficient magnetofection, miR-125b successfully shows a parallel effect on both M1, promoting polarization by targeting interferon regulatory factor 4 (IRF4) in macrophages, and tumor cell inhibition, by targeting ETS proto-oncogene 1 and cyclin- J...
November 5, 2020: Nanoscale
Aaron T Irving, Qian Zhang, Pui-San Kong, Katarina Luko, Pritisha Rozario, Ming Wen, Feng Zhu, Peng Zhou, Justin H J Ng, Radoslaw M Sobota, Lin-Fa Wang
Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner...
November 3, 2020: Cell Reports
Yan Yu, Lingling Cheng, Zhiyong Xu, Yanhong Zhang, Changbo Ou, Qiuxia Wang, Pei Gao, Jinyou Ma
Interferon regulatory factors (IRFs) are a family of transcription factors that play a role in a variety of biological processes including immune regulation of interferon and expression of inflammatory cytokines. However, the data on IRFs are rather limited in chickens. In the present study, qRT-PCR was used to study the tissue distribution of IRFs in chickens at D15 (the 15th day of raising) and developmental changes of all chIRFs (Chicken interferon regulatory factors) in BF from E15 (the 15th day of incubation) to D15...
October 30, 2020: Microbial Pathogenesis
Nicolas Maldonado, Fernanda Fredericksen, Constanza Espiñeira, Cristian Toledo, Jorge Oltra, Verónica de la Barra, Carolina Fernandez, Javier Salvador, Melina Villalba, Víctor H Olavarría
The bovine viral diarrhea virus (BVDV-1) is a pathogen with the capacity to modulate the interferon type I system. To further investigate the effects of BVDV-1 on the production of the immune response, the Madin-Darby bovine kidney cell line was infected with the cytopathic CH001 field isolate of BVDV-1, and the IFNbeta expression profiles were analyzed. The results showed that cpBVDV-1 was able to induce the production of IFNbeta in a way similar to polyinosinic-polycytidylic acid, but with less intensity...
October 11, 2020: Molecular Immunology
Zebin Liao, Zhe Liu, Zhenyu Gong, Xuguang Hu, Yuanyuan Chen, Kun Cao, Hong Zhang, Lu Gan, Juxiang Chen, Yanyong Yang, Jianming Cai
OBJECTIVE: Patients receiving carbon-ion radiation therapy and astronauts exploring outer space are inevitably exposed to heavy ion radiation. The aim of this study was to develop radioprotectors to minimize the injuries induced by carbon ion radiation. METHODS: Heat-killed Salmonella Typhimurium (HKST) was administered to mice by gavage prior to irradiation with a 12 C6+ heavy ion accelerator. Hematoxylin and eosin staining and immunofluorescence TdT-mediated dUTP Nick-End Labeling staining were used to assess the radioprotective effect of HKST on organ damage and levels of apoptosis, respectively, in mice...
October 2020: Journal of International Medical Research
Oleg Kruglov, Xuesong Wu, Sam T Hwang, Oleg E Akilov
The therapy of advanced mycosis fungoides (MF) presents a therapeutic challenge, and the search for new therapeutic targets is ongoing. Poly(ADP-ribose) polymerase 1 was shown to be upregulated in patients with advanced MF and could be druggable by a new class of chemotherapeutic agents, PARP-1 inhibitors, which are already in clinical trials for other malignancies; however, the role of PARP-1 inhibitors in MF has never been established. We examined the efficacy of talazoparib in the murine model of cutaneous T-cell lymphoma...
October 13, 2020: Blood Advances
Bin Zhu, Tianbao Wang, Xiaoxia Wei, Yancai Zhou, Jiansheng Li
Plasmacytoid dendritic cells (pDCs) were treated with cytosine-phosphate-guanine (CpG) DNA, and cell apoptosis, signals and immune responses were measured to investigate the effects and mechanism of CpG DNA in pDCs from chronic hepatitis B patients. CpG DNA-stimulated pDCs secreted more IFN-α than the control pDCs. CpG DNA activated Toll-like receptor 9 (TLR9), thereby resulting in the upregulated expression of myeloid differentiation primary response gene 88 (MyD88), interferon regulatory factor 7 (IRF7) and nuclear factor kappa B (NF-κB)...
September 29, 2020: Archives of Physiology and Biochemistry
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