Frontiers in Immunology
·
2022
·
IF 8.786
Xin Zhao,Wenji Huang,Yanjie Shi,Jiahong Guo,Hehe Xiao,Ning Ji,Jianhua Feng,Huifeng Dang,Jun Zou
PLAAT1 is a member of the PLAAT protein family and plays important roles in tumor suppression, transglutaminase activation and peroxisomal biogenesis. Recently, PLAAT1 has been shown to promote degradation of p53 protein and cellular organelles such as mitochondria, endoplasmic reticulum and lysosome. In this study, we show that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Overexpression of Plaat1 in zebrafish cells suppresses antiviral responses and promotes virus replication. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to initiate degradation of IRF3 and IRF7, which can be attenuated by 3-methyladenine, an inhibitor of autophagosome. Our study provides novel insights into the functions of PLAAT1 in host immune response to viral infection.
研究领域:
免疫学
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病毒学
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分子生物学
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DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2024
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IF 10.3
Bingli Zhang,Yizhou Zhong,Jiaxin Du,Rongyi Ye,Bingchi Fan,Yanhong Deng,Ruobing Bai,Yu Feng,Xiaohong Yang,Yuji Huang,Boxuan Liang,Jiewei Zheng,Weifeng Rong,Xingfen Yang,Zhenlie Huang
1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.
研究领域:
环境毒理学
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生殖生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2026
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IF 4.8
Shiyao Feng,Boyu Sun,Longlong Tian,Mingkang Li,Guozhu Sun
Traumatic brain injury (TBI) is one of the most prevalent neurological disorders and a major cause of death and disability worldwide. Cuproptosis is a recently identified form of cell death. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that has been widely investigated in TBI, may contribute to the regulation of cuproptosis. In this study, we investigated the role of cuproptosis in TBI and the regulatory mechanisms of Nrf2. We found that cuproptosis was induced following TBI in both patients and mouse models. In TBI mice, cuproptosis peaked at 3 days post-injury and predominantly occurred in neurons. Nrf2 deficiency aggravates neuronal cuproptosis after TBI, primarily through IRF7-mediated upregulation of SLC31A1. The Nrf2 activator dimethyl fumarate (DMF) suppresses neuronal injury and improves neurological function in TBI mice by inhibiting cuproptosis. Our results establish that cuproptosis is an important mechanism in TBI and that activation of Nrf2 mitigates TBI-induced cuproptosis by regulating the IRF7–SLC31A1 axis.
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PubMed
高影响因子
ULTRASONICS SONOCHEMISTRY
·
2024
·
IF 8.7
Ying Pan,Chunjuan Liu,Shuo Jiang,Lili Guan,Xinyao Liu,Liankui Wen
In the current study, a novel crude polysaccharide (cNCEP) was extracted from N. commune Vaucher utilizing ultrasonic-assisted extraction (UAE) with 60 % ethanol, employing response surface methodology. The optimal yield of cNCEP was determined to be 8.07 ± 0.08 mg/g, achieved through ultrasonic-assisted extraction under the conditions of a material-to-liquid ratio of 1:22, temperature of 56 °C, power of 570 W, and duration of 147 min. Subsequent purification of NCEP via Sephadex G75 resulted in a novel polysaccharide with a molecular weight of 20.466 kDa. NCEP exhibited significant scavenging activites against DPPH and hydroxyl radicals, as well as notable in vitro immunomodulatory properties. Furthermore, the mechanisms underlying the immunomodulatory effects of NCEP, involving enhancement of immunity, were investigated, revealing potential regulation of MAPK and TLR4-IRF7-NF-κB signaling pathways through RNA-Seq and Western blot analyses. These findings highlight the promising potential of NCEP as an organic immunomodulatory agent and functional food ingredient.
研究领域:
生物化学
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免疫学
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药理学
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食品科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yiting Yang,Ping Ren,Ying Sun,Junyi Li,Xinjun Zhou,Haipeng Zhang,Chengguang He,Huining Dai,Lili Guan
Nostoc commune Vaucher, a terrestrial and benthic blue-green alga, widely used in food and medicine worldwide. N. commune Polysaccharides (NCVP) have excellent biological activities, especially immunomodulatory, hypoglycemic and anti-tumor activities. However, the mechanism and structure-activity relationship of NCVP has been less studied. In this study, based on methylation and NMR results, a novel polysaccharide NCVP2 with 135 kDa, containing→4)-α-D-Gal p -(1→, → 4)-β-D-Glc p -(1→, and →4)-α-D-Xyl p -(1→ residues as the backbon, was sequentially purified from N.commune by DEAE-52 and Sephadex G-100 column. NCVP2 (50 μg/mL) exhibited the strong in vitro immunomodulatory activity by promoting the generation of nitric oxide ( NO ) and reactive oxygen species (ROS). A total of 2048 differentially expressed genes (DEGs) were identified by RNA-seq, including 1019 down-regulated genes and 1065 up-regulated genes. These DEGs were mainly enriched in the immune-related biological processes, involving in Mitogen-activated protein kinase (MAPK) and Toll-like receptor (TLR) signaling pathways by GO and KEGG enrichment analysis. Furthermore, Western blot results proved NCVP2 could recognize TLR2 and TLR4/MD2, and regulate TLR7/IRF7, MAPK and PI3K/AKT signaling pathways. In summary, a novel polysaccharide NCVP2 from N.commun e was proposed to exhibit significant immunomodulatory effects with multiple-paths and targets, and has great potential in the development of healthy foods such as immunomodulators.
研究领域:
免疫学
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生物化学
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药理学
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分子生物学
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植物科学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
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IF 8.786
Zhang Nan,Gao Xiaochen,Zhang Weijia,Xiong Junyao,Cao Xiaojian,Fu Zhen F.,Cui Min
Japanese encephalitis virus (JEV) is one of the most important members of the flavivirus family. It is a typical zoonotic pathogen that has caused substantial social and economic losses worldwide. The relation between JEV-induced immunosuppression and inflammatory responses has not been thoroughly investigated. In this study, cells infiltrating the brain tissue of JEV-infected mice were mainly identified as monocytic myeloid-derived suppressor cells (M-MDSCs), which subsequently differentiated into CD3+ macrophages. Co-culture with T cells showed that both splenic M-MDSCs and brain infiltrated M-MDSCs isolated from JEV-infected mice inhibited T cell proliferation through ARG1 and iNOS. The splenectomy model revealed that JEV-induced M-MDSCs were mainly derived from bone marrow and migrated to the spleen and central nervous system (CNS). The results of the transcriptome analysis and IRF7-deficient mice indicated that the ZBP1-IRF7 signaling pathway stimulated by JEV RNA played a central role in the induction of M-MDSCs. M-MDSCs migrated into the CNS through the chemokine CCL2/N-CCL2 derived from astrocytes and brain infiltrated M-MDSCs differentiated into CD3+ macrophages through a mechanism mediated by M-CSF, IL-6 and IFN-γ in the brain microenvironment. These findings provide evidence for the mechanism that JEV regulates the differentiation of M-MDSCs and thereby exacerbates pathogenicity, which represents a potential therapeutic target for Japanese encephalitis (JE).
研究领域:
免疫学
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神经病毒学
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病毒学
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致病机制
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DOI
PubMed
高影响因子
ARCHIVES OF VIROLOGY
·
2024
·Vol. 169
·期 11
·1-10
·
IF 2.5
Jiao Qian,Zhu Shu,Liao Baolin,Liu Huiyuan,Guo Xiaoyan,Wu Lina,Chen Chuming,Peng Liang,Xie Chan
NLR family member X1 (NLRX1) is an important member of the NOD-like receptor (NLR) family and plays unique roles in immune system regulation. Patients with hepatitis B virus (HBV) infection are more likely to have the NLRX1 mutation p.Arg707Cys than healthy individuals. It has been reported that NLRX1 increases the infection rate of HBV in HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). However, the role of NLRX1 mutation ( p.Arg707Cys ) in hepatitis remains unclear. We constructed Huh7 cells that stably overexpressed NTCP, using LV003 lentivirus. First, wild-type (WT) and mutant (MT) NLRX1 overexpression plasmids were constructed. The MT plasmid contained a point mutation at position 707 of the WT overexpression plasmid. Then, Huh7-NTCP cells were transfected with the WT or MT NLRX1 overexpression plasmid, and subsequent NLRX1 expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. HBV RNA levels were determined using RT-qPCR. HBsAg and HBcAg levels were confirmed immunohistochemically. Interferon alpha (IFN-α), interleukin 6 (IL-6), and type I interferon beta (IFN-β) levels were determined using enzyme-linked immunosorbent assay kits. p-p65, p-interferon regulatory factor (IRF) 3, and p-IRF7 expression levels were examined using western blot. The interaction of NLRX1 and retinoic acid-inducible gene (RIG)-1/mitochondrial antiviral signaling (MAVS) protein was confirmed by coimmunoprecipitation. The interaction of NLRX1 with IFN-α, IL-6, or IFN-β was analyzed by dual luciferase reporter gene assay. The levels of HBV RNA, HBsAg, and HBcAg in infected cells transfected with the WT NLRX1 or MT NLRX1 expression plasmid were higher than those in the untransfected control group; and these levels were lower in the cells transfected with MT NLRX1 than in those transfected with WT NLRX1. The levels of IFN-α, IFN-β, IL-6, p-p65, p-IRF3, and p-IRF7 were lower in cells transfected with WT NLRX1 or MT NLRX1 than in control cells. The levels of IFN-β, p-p65, p-IRF3, and p-IRF7 were higher in cells transfected with MT NLRX1 than in those transfected with WT NLRX1. Moreover, NLRX1 competitively inhibited RIG1 binding to MAVS, but the mutation in MT NLRX1 reduced this inhibitory effect. In addition, NLRX1 decreased the promoter activity of IFN-α, IFN-β, and IL-6. Our findings revealed that NLRX1 is a regulatory factor that inhibits the anti-HBV ability of hepatocytes and that the mutation p.Arg707Cys in NLRX1 suppresses HBV infection and activates the IFN/nuclear factor κB pathway.
研究领域:
免疫学
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病毒学
·
分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Kai Yuan,Yiqi Yang,Yixuan Lin,Feng Zhou,Kai Huang,Shengbing Yang,Weiqing Kong,Fupeng Li,Tianyou Kan,Yao Wang,Caiqi Cheng,Yakun Liang,Haishuang Chang,Jie Huang,Haiyong Ao,Zhifeng Yu,Hanjun Li,Yihao Liu,Tingting Tang
The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
研究领域:
细胞生物学
·
干细胞研究
·
组织工程
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再生医学
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生物医学工程
·
传染病学
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PubMed
高影响因子
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