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1.
Front Plant Sci ; 15: 1358309, 2024.
Article in English | MEDLINE | ID: mdl-38711611

ABSTRACT

The study explores the impact of mine grassland restoration on plant communities and soil properties in alpine grasslands, a subject of significant interest due to the observed relationship between grassland changes, plant communities, and soil properties. While prior research has mainly focused on the consequences of grassland degradation on plant diversity and soil characteristics, the specific effects of varying restoration degrees in alpine mining grasslands at the regional scale remain poorly understood. To address this knowledge gap, we established 15 sampling plots (0.5m×0.5m) across five different restoration degrees within alpine mining grasslands in the Qilian Mountains, China. Our objective was to assess the variations in plant diversity and soil properties along these restoration gradients. We conducted comprehensive analyses, encompassing soil properties [soil water content (SWC), available nitrogen (AN), total phosphorus (TP), nitrate nitrogen (NO3-N), ammonium nitrogen (NH4-N), total nitrogen (TN), available phosphorus (AP), soil organic carbon (SOC), nitrate nitrogen, soil pH, and electrical conductivity (EC)], plant characteristics (height, density, frequency, coverage, and aboveground biomass), and plant diversity indices (Simpson, Shannon-Wiener, Margalef, Dominance, and Evenness indexes). Our findings included the identification and collection of 18 plant species from 11 families and 16 genera across the five restoration degrees: Very Low Restoration Degree (VLRD), Low Restoration Degree (LRD), Moderate Restoration Degree (MRD), High Restoration Degree (HRD), and Natural Grassland (NGL). Notably, species like Carex duriuscula, Cyperus rotundus, and Polygonum viviparum showed signs of recovery. Principal component analysis and Pearson correlation analysis revealed that soil pH, SWC, SOC, NO3-N, and AN were the primary environmental factors influencing plant communities. Specifically, soil pH and EC decreased as restoration levels increased, while SWC, AN, TP, NH4-N, TN, AP, SOC, and NO3-N exhibited a gradual increase with greater restoration efforts. Furthermore, the HRD plant community demonstrated similarities to the NGL, indicating the most effective natural recovery. In conclusion, our study provides valuable insights into the responses of plant community characteristics, plant diversity, and soil properties across varying restoration degrees to environmental factors. It also elucidates the characteristics of plant communities along recovery gradients in alpine grasslands.

2.
Adv Sci (Weinh) ; 11(12): e2306964, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38234236

ABSTRACT

The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti-infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano-micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug-loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano-micro composite called "CaP@MS-Oligo-Van" is synthesized. The porous CaP@MS-Oligo-Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS-Oligo-Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.


Subject(s)
Calcium Phosphates , Methicillin-Resistant Staphylococcus aureus , Osteomyelitis , Staphylococcal Infections , Humans , Staphylococcal Infections/drug therapy , Vancomycin/pharmacology , Vancomycin/therapeutic use , Anti-Bacterial Agents/pharmacology , Osteomyelitis/drug therapy , Osteomyelitis/microbiology
3.
Heliyon ; 9(12): e22690, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38107282

ABSTRACT

Artificial oasis is an important geographical unit that is formed by the combination of natural disturbances and human interventions in a fragile ecosystem of arid regions. Therefore, there are important theoretical and practical significance to estimate long term artificial oasis changes and its driving mechanism. We took Hexi Corridor in northwest of China as a case study, based on multi-types of data included documentary reconstruction records, historical archives data and published articles to quantitative analyze the relationship between artificial oasis evolution and a set of natural and human factors over the past two millennia (0-1990 AD). Results showed that artificial oases had a tortuous evolutionary history, experienced three periods of rapid development in the Hexi Corridor. The structural equation model revealed that two human related factors (population density and grain yield) have a significantly greater influence on artificial oasis development than natural variables (temperature). According to current conditions, paradigm shift in human behavior are the prerequisite for oasis evolution and its transition. Furthermore, assessment the scale of artificial oasis based on the human-land relationship is a future direction for research and practice, for allocating water and soil resources rationally, improving the quality of oasis, and controlling the scale of oasis.

4.
Biochem Pharmacol ; 213: 115614, 2023 07.
Article in English | MEDLINE | ID: mdl-37209857

ABSTRACT

Acute myocardial infarction (MI) and chemotherapeutic drug administration can induce myocardial damage and cardiomyocyte cell death, and trigger the release of damage-associated molecular patterns (DAMPs) that initiate the aseptic inflammatory response. The moderate inflammatory response is beneficial for repairing damaged myocardium, while an excessive inflammatory response exacerbates myocardial injury, promotes scar formation, and results in a poor prognosis of cardiac diseases. Immune responsive gene 1 (IRG1) is specifically highly expressed in activated macrophages and mediates the production of tricarboxylic acid (TCA) cycle metabolite itaconate. However, the role of IRG1 in the inflammation and myocardial injury of cardiac stress-related diseases remains unknown. Here, we found that IRG1 knockout mice exhibited increased cardiac tissue inflammation and infarct size, aggravated myocardial fibrosis, and impaired cardiac function after MI and in vivo doxorubicin (Dox) administration. Mechanically, IRG1 deficiency enhanced the production of IL-6 and IL-1ß by suppressing the nuclear factor red lineage 2-related factor 2 (NRF2) and activating transcription factor 3 (ATF3) pathway in cardiac macrophages. Importantly, 4-octyl itaconate (4-OI), a cell-permeable derivative of itaconate, reversed the inhibited expression of NRF2 and ATF3 caused by IRG1 deficiency. Moreover, in vivo 4-OI administration inhibited the cardiac inflammation and fibrosis, and prevented adverse ventricle remodeling in IRG1 knockout mice with MI or Dox-induced myocardial injury. Our study uncovers the critical protective role of IRG1 in suppressing inflammation and preventing cardiac dysfunction under ischemic or toxic injury conditions, providing a potential target for the treatment of myocardial injury.


Subject(s)
Myocardial Infarction , NF-E2-Related Factor 2 , Animals , Mice , Doxorubicin , Inflammation/metabolism , Mice, Knockout , NF-E2-Related Factor 2/metabolism
5.
Sci Total Environ ; 880: 163285, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37028658

ABSTRACT

Previous studies have quantified the contributions of climate factors, vegetation, and terrestrial water storage change, and their interaction effects on hydrological process variation within the Budyko framework; however, further decomposition of the contributions of water storage change has not been systematically investigated. Therefore, focusing on the 76 water tower units of the world, the annual water yield variance was first examined, followed by the contributions of changes in climate, water storage change, and vegetation, as well as their interaction effects on water yield variance; finally, the contribution of water storage change on water yield variance was further decomposed into the effect of changes in groundwater, snow water, and soil water. The results showed that large variability exists in the annual water yield with standard deviations ranging from to 10-368 mm in water towers globally. The water yield variability was primarily controlled by the precipitation variance and its interacted effect with water storage change, with the mean contributions of 60 % and 22 %, respectively. Among the three components of water storage change, the variance in groundwater change had the largest effect on water yield variability (7 %). The improved method helps separate the contribution of water storage components to hydrological processes, and our results highlight that water storage changes should be considered for sustainable water resource management in water-tower regions.

6.
Sci Total Environ ; 865: 161106, 2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36586674

ABSTRACT

Recharge sources such as precipitation, mountain front recharge, mountain block recharge and confined water are the sources usually considered in quantitative studies of groundwater recharge. Changes in recharge processes caused by irrigation practices need to be fully considered for the accurate budgeting and management of water resources. Here, we put forward a conceptual framework for evaluating the shallow groundwater recharge process in arid irrigated agricultural areas using hydrochemical and stable isotope techniques, combined with an assessment of hydrogeological conditions and quantitative models. In general, the recharge effect of atmospheric precipitation on shallow groundwater in arid areas is relatively small. The contributions made by recharge sources in the studied river irrigated area, from greater to smaller, were confined groundwater (46.98 %), river water (45.48 %) and precipitation (7.55 %). The original range in groundwater recharge levels caused by river leakage also appeared to have expanded in response to the establishment of canal irrigation networks. Lateral groundwater flow and confined groundwater were the main recharge sources of shallow groundwater in areas fed by well irrigation and well-/spring-water irrigation (not taking into account any groundwater irrigation leakage). However, had the recharge of shallow groundwater by groundwater irrigation leakage, which reached 19.8-41.1 %, not been counted as contributing to actual groundwater recharge, the recharge contributions made by lateral groundwater flow and confined groundwater to shallow groundwater would have been significantly overestimated. This is because the groundwater recharge process has been modified by the various irrigation measures employed in arid agricultural areas, leading to a redistribution effect in groundwater recharge source contributions. This study provides a new perspective and intuitive data support for the development and utilization of water resources in arid regions.

7.
Sci Total Environ ; 855: 158940, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36152856

ABSTRACT

The land use and land cover change (LUCC) associated with climate change and human activities is supposed to exert a significant effect on ecosystem functions in arid inland regions. However, the role of LUCC in shaping the spatio-temporal patterns of ecosystem services and ecological security remain unclear, especially under different future LUCC scenarios. Here, we evaluated dynamic changes of ecosystem services and ecological security pattern (ESP) in the Hexi Regions based on LUCC and other environment variables by integrating morphological spatial pattern analysis (MSPA), entropy weight method and circuit theory. Our result showed that the LUCC was generally stable from 1980 to 2050. Compare to 2020, the land conversion under natural growth (NG), ecological protection (EP) and urban development (UD) scenarios in 2050 has changed by 10.30 %, 10.10 %, and 10.31 %, respectively. The forest, medium-cover grassland and water increased in the EP scenario, and construction land and cropland greatly expanded in the other two scenarios. Ecosystem services grew larger in the EP scenario by 2050 in comparison with the NG and UD scenarios. The ESP in the Hexi Regions has obvious spatial differences during 1980-2050. The larger ecological sources and less resistance corridors were mainly distributed in the central and eastern of the Hexi Regions with high ecosystem services. Conversely, fragmented ecological sources and larger resistance corridors were mostly located in the western regions blocked by sandy land, bare land or mountains. Compared to 2020, the area of ecological sources and pinch points under the EP scenario in 2050 increased by 4.10 × 103 km2 and 0.31 × 103 km2, respectively. The number of ecological corridors reduced while the length and resistance increased apart from the EP scenario. Our results highlighted the importance of ecological protection in shaping the LUCC, which further enhances the integrity of ecosystem and ecological security.


Subject(s)
Conservation of Natural Resources , Ecosystem , Humans , Forests , China , Climate Change
8.
Sci Total Environ ; 831: 154722, 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35339552

ABSTRACT

Forecasting river water levels or streamflow water levels (SWL) is vital to optimising the practical and sustainable use of available water resources. We propose a new deep learning hybrid model for SWL forecasting using convolutional neural networks (CNN), bi-directional long-short term memory (BiLSTM), and ant colony optimisation (ACO) with a two-phase decomposition approach at the 7-day, 14-day, and 28-day forecast horizons. The newly developed CBILSTM method is coupled with complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and variational mode decomposition (VMD) methods to extract the most significant features within predictor variables to build a hybrid CVMD-CBiLSTM model. We integrate three distinct datasets (satellite-derived, climate mode indices, and ground-based meteorological observations) to improve the forecasting capability of the CVMD-CBiLSTM model, applied at nineteen different gauging stations in the Australian Murray River system. This proposed model returns a significantly accurate performance with ~98% of all prediction errors within less than ±0.020 m and a low relative root mean square of ~0.08%, demonstrating its superiority over several benchmark models. The results show that using the new hybrid deep learning algorithm with ACO feature selection can significantly improve the accuracy of forecasted river water levels, and therefore, the method is attractive for adopting remote sensing data to the model ground-based river flow for strategic water savings planning initiatives and dealing with climate change-induced extreme events such as drought events.


Subject(s)
Deep Learning , Rivers , Australia , Forecasting , Neural Networks, Computer , Water
9.
J Environ Manage ; 312: 114911, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35305354

ABSTRACT

Soil organic carbon (SOC) storage in arid inland regions is significantly affected by land use and land cover change (LUCC) associated with climate change and agricultural activities. A systematic evaluation to the LUCC effects on SOC storage could enable us to better manage soil carbon pools in arid inland regions. Here, we evaluated the effects of LUCC on SOC storage in the Hexi Regions based on high-resolution SOC and LUCC maps derived from Landsat imagery and digital soil mapping using machine learning algorithm and environmental covariates. The results showed that SOC generally increased from northwest to southeast over the Hexi Regions with an average stock of 7.15 kg C m-2 at a soil depth of 100 cm and a total storage of 2783.05 Tg C. The SOC stock and storage in the Qilian Mountains (mountains) was about 3.90 and 4.55 times higher than that in the Hexi Corridor (plains), respectively. It was estimated that LUCC over the past four decades caused a net increase of 23.41 and 18.19 Tg C in total SOC storage for the Qilian Mountains and Hexi Corridor, respectively. Specifically, the development in grasslands quality as well as the land-use category conversion from the bare land to grassland mainly contributed to the increase in SOC storage of the Qilian Mountains, where the LUCC was mainly driven by climate change. By contrast, the SOC storage change in the Hexi Corridor was mainly associated with the conversion from sandy land and low-cover grassland to cropland as well as sandy land to grassland, being mainly affected by intense cropland expansion and desertification control. Our results highlighted the importance of climate change and cropland expansion in enhancing SOC storage of the Qilian Mountains and Hexi corridor, respectively.


Subject(s)
Carbon , Soil , Agriculture , Carbon/analysis , Carbon Sequestration , China , Desert Climate
10.
Sci Total Environ ; 759: 143532, 2021 Mar 10.
Article in English | MEDLINE | ID: mdl-33250260

ABSTRACT

Terrestrial evapotranspiration (ETa) reflects the complex interactions of climate, vegetation, soil and terrain and is a critical component in water and energy cycles. However, the manner in which climate change and vegetation greening influence ETa remains poorly understood, especially in alpine regions. Drawing on the Global Land Evaporation Amsterdam Model (GLEAM) ETa data, the interannual variability of ETa and its ties to precipitation (P), potential evaporation (ETp) and vegetation (NDVI) were analysed. The Budyko framework was implemented over the period of 1982 to 2015 to quantify the response of ETa to climate change's direct (P and ETp) and indirect (NDVI) impacts. The ETa, P, ETp and NDVI all showed significant increasing trends from 1981 to 2015 with rates of 1.52 mm yr-1, 3.18 mm yr-1, 0.89 mm yr-1 and 4.0 × 10-4 yr-1, respectively. At the regional level, the positive contribution of increases in P and NDVI offset the negative contribution of ETp to the change in ETa (∆ETa). The positive ∆ETa between 1982 and 2001 was strongly linked with the concomitant increase in NDVI. Increases in vegetation contributing to a positive ∆ETa differed among landscape types: for shrub, meadow and steppe they occurred during both periods, for alpine vegetation between 1982 and 2001, and for desert between 2002 and 2015. Climate change directly contributed to a rise in ETa, with P as the dominant factor affecting forested lands during both periods, and alpine vegetation between 2002 and 2015. Moreover, ETp was a dominant factor for the desert between 1982 and 2001, where the variation of P was not significant. The contributions of factors having an impact on ∆ETa are modulated by both the sensitivity of impact factors acting on ETa as well as the magnitudes of factor changes. The greening of vegetation can influence ETa by increasing vegetation transpiration and rainfall interception in forest, brush and meadow landscapes. These findings can help in developing a better understanding of the interaction of ecosystems and hydrology in alpine regions.


Subject(s)
Climate Change , Ecosystem , China , Water
11.
Exp Ther Med ; 20(4): 3221-3227, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32855691

ABSTRACT

The present study aimed to clarify the influence of long non-coding RNA small nuclear host gene 16 (lncRNA SNHG16) on cardiomyocyte proliferation following ischemia/reperfusion injury (IRI) and the potential mechanism. An IRI model in mice was established by performing ligation of the anterior descending coronary artery (LAD). Primary cardiomyocytes were isolated from newborn mice and subjected to H2O2 treatment to mimic in vitro IRI. Relative levels of SNHG16 and miRNA-770-5p in both in vivo and in vitro IRI models were examined. The regulatory effects of SNHG16 and miRNA-770-5p on the proliferative ability of H2O2-treated cardiomyocytes were assessed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assay. The binding relationship between SNHG16 and miRNA-770-5p was verified through dual-luciferase reporter gene assay. It is found that SNHG16 was time-dependently downregulated in the IRI models. Overexpression of SNHG16 enhanced the proliferative ability of the cardiomyocytes. miRNA-770-5p was found to be a direct target of SNHG16. Moreover, SNHG16 was able to negatively regulate the miRNA-770-5p level. Overexpression of miRNA-770-5p partially reversed the role of SNHG16 on accelerating cardiomyocyte proliferation. Collectively, SNHG16 accelerates the proliferative ability of cardiomyocytes following IRI by negatively regulating miRNA-770-5p.

12.
Heart Lung Circ ; 29(8): 1203-1209, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32059950

ABSTRACT

AIM: The aim of this study was to investigate the effect of the modified extracorporeal circulation perfusion method during surgery for acute Stanford type A aortic dissection in patients who underwent stented elephant trunk implantation and arch replacement. METHOD: A total of 69 patients with acute Stanford type A aortic dissection who underwent stented elephant trunk implantation and arch replacement were retrospectively analysed from 2017 to 2018. According to the perfusion method of extracorporeal circulation, patients were divided into a routine perfusion (RP) group and a modified perfusion (MP) group. Clinical data were collected, including the time of extracorporeal circulation and deep hypothermic circulatory arrest, incidence of acute kidney injury and neurological complications, and comparisons between the two groups were conducted by using independent sample t-tests for normally distributed qualitative data, the Mann-Whitney U-test for skewed qualitative data, and the chi square test or Fisher's exact test for categorical data. RESULTS: There were 55 (80%) males and 14 (20%) females in the entire cohort, and the mean ± standard deviation age was 50.4±9.0 years. A total of 53 (77%) patients were included in the RP group, and 16 (23%) were included in the MP group. Patients in the MP group were older (55.5±7.8 vs 48.8±8.9 years), and the difference was significant (p=0.008). Compared with the RP group, the time of extracorporeal circulation (218.0 [44.7] vs 246.0 [58.0] min; p=0.005) and deep hypothermic circulatory arrest (4.0 [2.0] vs 25.0 [10.0] min; p<0.001) was shorter, and the incidence of postoperative acute kidney injury (n=6 [37.5%] vs n=36 [67.9%]; p=0.029) was lower in the MP group; the differences were significant. Six (6) patients died in the RP group; no patients died in the MP group. The total in-hospital mortality rate was 8.7%. CONCLUSIONS: The modified extracorporeal circulation perfusion method is feasible, with satisfactory results.


Subject(s)
Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation/methods , Extracorporeal Circulation/methods , Perfusion/methods , Acute Disease , Aortic Dissection/mortality , Aortic Aneurysm, Thoracic/mortality , China/epidemiology , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome
13.
Sci Total Environ ; 713: 136587, 2020 Apr 15.
Article in English | MEDLINE | ID: mdl-31955092

ABSTRACT

The relationship between climate and human society has frequently been investigated to ascertain whether climate variability can trigger social crises (e.g., migration and armed conflicts). In the current study, statistical methods (e.g., correlation analysis and Granger Causality Analysis) are used in a systematic analysis of the potential causality of climate variability on migration and armed conflicts. Specifically, the statistical methods are applied to determine the relationships between long-term fine-grained temperature and precipitation data and contemporary social conditions, gleaned from historical documents covering the last two millennia in China's Hexi Corridor. Results found the region's reconstructed temperature to be strongly coupled with precipitation dynamics, i.e., a warming climate was associated with a greater supply of moisture, whereas a cooling period was associated with more frequent drought. A prolonged cold period tended to coincide with societal instability, such as a shift from unification towards fragmentation. In contrast, a prolonged warm period coincided with rapid development, i.e., a shift from separation to unification. The statistical significance of the causality linkages between climate variability, bio-productivity, grain yield, migration and conflict suggests that climate variability is not the direct causative agent of these phenomena, but that climate reduced food production which gradually lead to migration and conflicts. A conceptual causal model developed through this study describes the causative pathway of climate variability impacts on migration and conflicts in the Hexi Corridor. Applied to current conditions, the model suggests that steady and proactive promotion of the nation's economic buffering capacity might best address the uncertainty brought on by a range of potential future climate scenarios and their potential impacts.

14.
Cell Death Dis ; 9(7): 769, 2018 07 10.
Article in English | MEDLINE | ID: mdl-29991775

ABSTRACT

The excessive inflammation triggered by damage-associated molecular patterns (DAMPs) after myocardial infarction (MI) is responsible for the development of cardiac dysfunction and adverse remodeling, while the mechanisms by which inflammation is fine tuned remain to be fully elucidated. MicroRNA-21 (miR-21) has been shown to function in cardiovascular diseases, while its role in inflammatory responses and cardiac function post MI in mice remains unknown. Here, we found that miR-21 expression was markedly increased in border and infarct areas of cardiac tissues during the early inflammatory phase of MI model established by ligating the left-anterior descending coronary artery. MiR-21 knockout mice had decreased survival rates, worse cardiac dysfunction, and increased infarct and scar areas after MI compared with WT mice. MiR-21 knockout mice showed significantly higher levels of inflammatory cytokines including IL-1ß, IL-6, and TNF-α in cardiac tissues, as well as infiltration of CD11b+ monocytes/macrophages with higher expression level of inflammatory cytokines. MI induced the great release of high mobility group protein B1 (HMGB1) and heat shock protein 60 (HSP60) in cardiac tissue. MiR-21 deficiency significantly promoted the inflammatory cytokine production triggered by DAMPs in macrophages, whereas, miR-21 overexpression markedly inhibited the inflammatory cytokine production. Mechanistically, miR-21 deficiency enhanced p38 and NF-κB signaling activation in cardiac tissue post MI and macrophages treated with DAMPs. MiR-21 was found to directly target kelch repeat and BTB (POZ) domain containing 7 (KBTBD7), which promoted DAMP-triggered inflammatory responses in macrophages. Furthermore, KBTBD7 interacted with MKK3/6 and promoted their activation, which in turn enhanced the activation of downstream p38 and NF-κB signaling induced by DAMPs. Therefore, our findings demonstrate that miR-21 attenuates inflammation, cardiac dysfunction, and maladaptive remodeling post MI through targeting KBTBD7 and inhibiting p38 and NF-κB signaling activation, suggesting that miR-21 may function as a novel potential therapeutic target for MI.


Subject(s)
Inflammation/metabolism , MicroRNAs/metabolism , Myocardial Infarction/metabolism , Proteins/metabolism , Alarmins/metabolism , Animals , Inflammation/genetics , Inflammation/pathology , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Intracellular Signaling Peptides and Proteins , MAP Kinase Kinase 3/metabolism , MAP Kinase Kinase 6/metabolism , Macrophages/metabolism , Male , Mice , Mice, Knockout , MicroRNAs/genetics , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Protein Binding , Random Allocation , Signal Transduction/genetics , Signal Transduction/physiology , Tumor Necrosis Factor-alpha/metabolism
15.
J Immunol ; 195(8): 3849-57, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26363053

ABSTRACT

The effective recognition of viral infection and subsequent type I IFN production is essential for the host antiviral innate immune responses. The phosphorylation and activation of kinase TANK-binding kinase 1 (TBK1) plays crucial roles in the production of type I IFN mediated by TLR and retinoic acid-inducible gene I-like receptors. Type I IFN expression must be tightly regulated to prevent the development of immunopathological disorders. However, how the activated TBK1 is negatively regulated by phosphatases remains poorly understood. In this study, we identified a previously unknown role of protein phosphatase (PP)4 by acting as a TBK1 phosphatase. PP4 expression was upregulated in macrophages infected with RNA virus, vesicular stomatitis virus, and Sendai virus in vitro and in vivo. Knockdown of PP4C, the catalytic subunit of PP4, significantly increased type I IFN production in macrophages and dentritic cells triggered by TLR3/4 ligands, vesicular stomatitis virus, and Sendai virus, and thus inhibited virus replication. Similar results were also found in peritoneal macrophages with PP4C silencing in vivo and i.p. infection of RNA virus. Accordingly, ectopic expression of PP4C inhibited virus-induced type I IFN production and promoted virus replication. However, overexpression of a phosphatase-dead PP4C mutant abolished the inhibitory effects of wild-type PP4C on type I IFN production. Mechanistically, PP4 directly bound TBK1 upon virus infection, then dephosphorylated TBK1 at Ser(172) and inhibited TBK1 activation, and subsequently restrained IFN regulatory factor 3 activation, resulting in suppressed production of type I IFN and IFN-stimulated genes. Thus, serine/threonine phosphatase PP4 functions as a novel feedback negative regulator of RNA virus-triggered innate immunity.


Subject(s)
Gene Expression Regulation/immunology , Immunity, Innate , Interferon Type I/immunology , Phosphoprotein Phosphatases/immunology , Respirovirus Infections/immunology , Rhabdoviridae Infections/immunology , Sendai virus/physiology , Vesiculovirus/physiology , Virus Replication/immunology , Animals , Dendritic Cells/immunology , Dendritic Cells/pathology , Macrophages/immunology , Macrophages/pathology , Mice , Phosphorylation/immunology , Protein Serine-Threonine Kinases/immunology , Respirovirus Infections/pathology , Rhabdoviridae Infections/pathology
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