Journal of Inflammation Research
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2023
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IF 4.5
Yunbo Yan,Linqian Yu,Binyang Chen,Chang’an Cao,Hairong Zhao,Qiang Wang,De Xie,Yuemei Xi,Chenggui Zhang,Jidong Cheng
Background Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation.Methods PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals.Results Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1β release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1β production.Conclusion Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.
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Journal of Immunology Research
·
2021
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IF 4.818
Lin Zhang,Lukun Yang,Xiaowei Xie,Hongyue Zheng,Hangsheng Zheng,Lizong Zhang,Cuizhe Liu,Ji-Gang Piao,Fanzhu Li
Baicalin (BA) magnesium salt (BA-Mg) is a good water-soluble ingredient extracted from Scutellaria baicalensis Georgi, a commonly used traditional Chinese medicine. This study is aimed at investigating whether BA-Mg could exert a better protective effect on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and illuminate the underlying mechanisms in vivo and in vitro. Mice were intraperitoneally administrated with equimolar BA-Mg, BA, and MgSO4 before LPS inducing ALI. Lung tissues and bronchoalveolar lavage fluid were collected for lung wet/dry ratio, histological examinations, cell counts, and biochemical analyses at 48 h post-LPS exposure. Meanwhile, the protein expressions of TLR4/NF-κB signaling pathway and proinflammatory cytokines in lung tissues and lung bronchial epithelial cells (BEAS-2B) were detected. The results showed BA-Mg pronouncedly ameliorated LPS-induced inflammatory response and histopathological damages, elevated antioxidant enzyme activity (SOD), and downregulated myeloperoxidase (MPO) and malonaldehyde (MDA) levels through the inhibition of TLR4/NF-κB signaling pathway activation. Moreover, the effect of BA-Mg was significantly better than that of BA and MgSO4 in ameliorating symptoms. Overall, BA-Mg can effectively relieve inflammatory response and oxidative stress triggered by LPS, indicating it may be a potential therapeutic candidate for treating ALI.
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Oxidative Medicine and Cellular Longevity
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2021
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IF 6.543
Zhenling Zhang,Lijing Zhang,Qiuping Zhang,Bojia Liu,Fang Li,Yi Xin,Zhijun Duan
Background. Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss. Materials and Methods. We induced gut leakiness by injecting carbon tetrachloride (CCl4) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor-α (TNF-α) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro. Results. Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF-α levels; upregulated tight junction (TJ) expression; and inhibited epithelial IκB-α degradation and phosphorylation, NF-κB p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl4. Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro, using Caco-2 cells with gain- or loss-of-HO-1-function after TNF-α. Pretreated with JSH-23 (NF-κB inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF-α-induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF-κB p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury. Conclusion. HO-1/CO maintains intestinal barrier integrity through the NF-κB/MLCK pathway. Therefore, the intestinal HO-1/CO-NF-κB/MLCK system is a potential therapeutic target for diseases with a leaky gut.
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BIOSENSORS & BIOELECTRONICS
·
2020
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IF 10.257
Kai Zhang,Zhenqiang Fan,Bo Yao,Tingting Zhang,Yuedi Ding,Sha Zhu,Minhao Xie
2019 novel coronavirus (2019-nCoV) with strong contagion in the crowd, has ravaged worldwide and severely impacts the human health and epidemic prevention system, by producing a series of significant stress reactions in the body to induce further cytokine storm. Transcription factors (TFs) served as essential DNA binding proteins play an integral role in regulating cytokine storm, and the detection of it in the human coronavirus environment provides especially valuable approaches to diagnosis and treatment of 2019-nCoV and development of antiviral drugs. In this work, an entropy-driven electrochemiluminescence (ECL) biosensor was constructed for ultra-sensitive bioassay of NF-κB p50. The strategy primarily capitalizing the splendid double-stranded DNA (dsDNA) binding properties of transcription factors, employing GOAu-Ru composite material as ECL emitter, utilizing entropy-driven reactions for signal amplification method, offered a repeatable proposal for TFs detection. In the absence of TFs, the released DNA1 further went in the entropy-driven reaction, contributing to an “ECL off” state. However, in the presence of TFs, the dsDNA avoided being digested, which blocked DNA1 for participating in the entropy-driven reaction, and the system exhibited an “ECL on” state. Most importantly, the ECL bioanalytical method denoted broad application prospects for NF-κB p50 detection with a lower detection limit (9.1 pM).
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Evidence-based Complementary and Alternative Medicine
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2020
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IF 1.813
Yang Zheng,Jiahui Wang,Jiaru Wang,Haiyuan Xie,Tiejian Zhao
Objective. To study the effect of curcumol on liver sinusoidal endothelial cells (LSECs) and to analyze the mechanism of antihepatic fibrosis. Methods. The effects of drug intervention on cell proliferation rates were detected by MTT assay. The expression of NF-κB was detected by RT-PCR and WB. The NF-κB expression and entry into the nucleus were detected by immunofluorescence; scanning electron microscopy was used to observe the changes of LSECs fenestrae. Results. MTT results showed that the interference of cell proliferation in each group was small. RT-PCR showed that the expression of NF-κB in the curcumol intervention group was significantly lower than that in the positive control group (). The WB detection found that, in the curcumol intervention group, the expression of pNF-κB in the NF-κB signaling pathway was significantly lower than that in the positive control group (). Scanning electron microscopy showed that the LSEC fenestrae were significantly improved compared with the positive control group. Conclusion. Curcumol may be one of the mechanisms of antihepatic fibrosis by inhibiting the activity of the NF-κB signaling pathway and increasing the fenestrae of LSECs.
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2021
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IF 3.228
Jianqing Chen,Bing Shao,Jinliang Wang,Zhiqiang Shen,Honggui Liu,Shu Li
Chlorpyrifos (CPF) is an organophosphate insecticide and can cause cell death of animals. In the study, the common carp were exposed to CPF at 0 μg/L (the control group), 1.16 μg/L (the low dose group), 11.6 μg/L (the medium dose group), and 116 μg/L (the high dose group), respectively. The carp were euthanized at the 30th day and gills were collected immediately. The ultrastructural and histopathological observations showed obvious necrosis characteristics and inflammatory injury in the CPF-treated groups. CPF exposure activated the MAPK pathway, in which the mRNA and protein expressions of extracellular signal-regulated (ERK), p38 MAP kinase (p38), and c-Jun N-terminal kinase (JNK) were increased; the mRNAs and proteins of NF-κB and TNF-α were activated; and the mRNAs and proteins of necroptosis related genes were changed (the mRNA and protein expression of RIPK1 , RIPK3 , MLKL, and FADD were increased and caspase-8 was decreased) with concentration dependency. Taken together, we concluded that CPF exposure activated the MAPK/NF-κB/TNF-α pathway, promoted inflammatory injure and evoked necroptosis in common carp gills. In addition, CPF-induced inflammation and necroptosis was concentration dependency. The toxic effects of CPF on gills provided data for both aquaculture and toxicological studies.
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INFECTION GENETICS AND EVOLUTION
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2021
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IF 3.342
M.A. Abo-Kadoum,Mohammed Assad,Moure UAE,Stech A.E. Nzaou,Zhen Gong,Asmaa Moaaz,Samson Teweldebrhan,Adel Eltoukhy,Ai Xuefeng,Yu Chen,Jianping Xie
Mycobacterium tuberculosis (Mtb) survival and virulence largely reside on its ability to manipulate the host immune response . We have previously shown that M. tuberculosis Raf kinase inhibitor protein (RKIP) Rv2140c regulates diverse phosphorylation events in M. smegmatis . However, its role during infection is unknown. In this report, we show that Rv2140c can mimic the mammalian RKIP function. Rv2140c inhibit the activation of extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) via decreasing the phosphorylation capacity of upstream mediators MEK1, ERK1/2, and IKKα/β, thus leading to a reduction in pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. This effect can be reversed by RKIP inhibitor locostatin. Furthermore Rv2140c mediates apoptosis associated with activation of caspases cascades. This modulation enhances the intracellular survival of M. smegmatis within macrophage. We propose that Rv2140c is a multifunctional virulence factor and a promising novel anti-Tuberculosis drug target.
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ACTA PHARMACOLOGICA SINICA
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2019
·Vol. 40
·期 8
·1019-1028
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IF 4.01
Yi Quan,Tan Fang-hui,Tan Jia-an,Chen Xiu-hui,Xiao Qing,Liu Ying-hua,Zhang Gui-ping,Luo Jian-dong
Minocycline is a tetracycline antibiotic and has been shown to play a protective role in cerebral and myocardial ischemia/reperfusion (I/R). However, the underlying mechanism remains unclear. Herein, we investigated whether monocyte chemotactic protein-induced protein-1 (MCPIP1), a negative regulator of inflammation, was involved in the minocycline-induced cardioprotection in myocardial I/R in vivo and in vitro models. Myocardial ischemia was induced in rats by left anterior descending coronary artery occlusion for 1 h and followed by 48 h reperfusion. Minocycline was administered prior to ischemia (45 mg/kg, ip, BID, for 1 d) and over the course of reperfusion (22.5 mg/kg, ip, BID, for 2 d). Cardiac function and infarct sizes were assessed. Administration of minocycline significantly decreased the infarct size, alleviated myocardial cell damage, elevated left ventricle ejection fraction, and left ventricle fractional shortening following I/R injury along with significantly decreased pro-inflammatory cytokine IL-1β and monocyte chemoattractant protein-1 (MCP-1) levels in heart tissue. H9c2 cardiomyocytes were subjected to oxygen glucose deprivation (OGD) followed by reoxygenation (OGD/R). Pretreatment with minocycline (1−50 μmol/L) dose-dependently increased the cell viability and inhibited OGD/R-induced expression of MCP-1 and IL-6. Furthermore, minocycline dose-dependently inhibited nuclear translocation of NF-κB p65 in H9c2 cells subjected to OGD/R. In both the in vivo and in vitro models, minocycline significantly increased MCPIP1 protein expression; knockdown of MCPIP1 with siRNA in H9c2 cells abolished all the protective effects of minocycline against OGD/R-induced injury. Our results demonstrate that minocycline alleviates myocardial I/R injury via upregulating MCPIP1, then subsequently inhibiting NF-κB activation and pro-inflammatory cytokine secretion.
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JOURNAL OF DRUG TARGETING
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2019
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IF 3.277
Yan Jiang,Hongjiao Du,Xue Liu,Xi Fu,Xiaodong Li,Qian Cao
There is increasing evidence that atherosclerosis is the significant risk factor for cardiovascular diseases, which are the leading causes of morbidity and mortality worldwide. Artemisinin is a natural endoperoxides quiterpene lactone compound in Artemisia annua L with vasculoprotective effects. The primary aim of this study was to investigate whether artemisinin could be conferred an anti-atherosclerotic effect in high-fat diet (HFD)-fed ApoE–/– mice and explore the possible mechanism. We found that treatment with artemisinin (50 and 100 mg/kg) effectively ameliorated atherosclerotic lesions, such as foam cell formation, hyperplasia and fibrosis in the aortic intima. Atherosclerotic mice treated with artemisinin showed reduced inflammation by up-regulating adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) activation and by down-regulating nuclear factor-κB (NF-κB) phosphorylation and nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome expression in the aortas. In addition, artemisinin was found to promote AMPK activity in macrophages and its anti-inflammatory effect was neutralised by AMPK silence using specific siRNA. In conclusion, we demonstrate that artemisinin may protect the aortas from atherosclerotic lesions by suppression of inflammatory reaction via AMPK/NF-κB/NLRP3 inflammasomes signalling in macrophages.
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Hepatology International
·
2019
·Vol. 14
·期 1
·145-160
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IF 5.49
Zhao Jing,Han Ming,Zhou Li,Liang Pu,Wang Yun,Feng Shenghu,Lu Hongping,Yuan Xiaoxue,Han Kai,Chen Xiaofan,Liu Shunai,Cheng Jun
Background This study aimed to investigate the roles and mechanisms of tenofovir alafenamide fumarate (TAF)/tenofovir disoproxil fumarate (TDF) in treating liver fibrosis. Methods The effects of TAF/TDF on carbon tetrachloride (CCl 4 )-induced liver fibrosis in C57BL/6 wild-type or nonstructural protein 5A transactivated protein 9 (NS5ATP9) knockout mice were studied. The differentiation, activation, and proliferation of LX-2 cells after TAF/TDF treatment were tested in vitro. The expression of NS5ATP9 and activities of transforming growth factor-β1 (TGFβ1)/Sekelsky mothers against decapentaplegic homolog 3 (Smad3) and NF-κB/NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were detected in TAF/TDF-treated mice and LX-2 cells. The genes related to extracellular matrix accumulation were detected in vivo and in vitro after NS5ATP9 silencing or knockout. Results TAF/TDF significantly inhibited CCl 4 -induced liver fibrosis in mice, and regulated the differentiation, activation, and proliferation of hepatic stellate cells (HSCs). Furthermore, TAF/TDF suppressed the activities of TGFβ1/Smad3 and NF-κB/NLRP3 inflammasome signaling pathways in vivo and in vitro. NS5ATP9 inhibited liver fibrosis through TGFβ1/Smad3 and NF-κB signaling pathways. TAF/TDF upregulated the expression of NS5ATP9 in vivo and in vitro. Finally, TAF/TDF could only show marginal therapeutic effects when NS5ATP9 was silenced and knocked out in vivo and in vitro. Conclusions TAF/TDF prevented progression and promoted reversion of liver fibrosis through assembling TGFβ1/Smad3 and NF-κB/NLRP3 inflammasome signaling pathways via upregulating the expression of NS5ATP9. TAF/TDF also regulated the differentiation, activation, and proliferation of HSCs. The findings provided strong evidence for the role of TAF/TDF as a new promising therapeutic strategy in liver fibrosis.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
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IF 2.559
Fan Zhang,Chenhong Zhang
Intracerebral hemorrhage (ICH) is reported as a common and often fatal type of stroke accompanied with high morbidity and mortality, and it frequently results in long-lasting neurological dysfunctions. However, the pathogenesis that contributes to ICH has not been fully understood. Rnf112, also known as Znf179, is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is modulated during brain progression and development. The study aimed to explore the role of Rnf112 in brain injury after ICH, as well as the underlying molecular mechanisms. The results indicated that ICH led to a significant decrease in Rnf112, which was confirmed in oxyhemoglobin (oxyHb)-incubated astrocytes and microglial cells. Moreover, the Rnf112 knockout (Rnf112 −/− ) mice and wild type (WT) mice induced by ICH were further employed. Compared to the WT/ICH group, Rnf112 −/− mice exhibited accelerated brain injury, as evidenced by the increased brain water contents and neurological deficit scores (NDS). In comparison to WT/ICH group, a remarkable up-regulation in the release of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was observed in perihematoma tissues of Rnf112 −/− mice on day 3 post-ICH. The process was along with promoted glial fibrillary acidic protein (GFAP) and Iba1 expression and reduced NeuN levels. Furthermore, ICH-induced increases in toll-like receptor (TLR)-4 and myeloid differentiation primary response protein (MyD88) expression were exacerbated by the loss of Rnf112. The phosphorylated expression of IKKα, inhibitor of NF-κB (IκBα) and nuclear factor-kappa B (NF-κB) induced by ICH in perihematoma tissues of mice was markedly enhanced in Rnf112 −/− mice. Rnf112 repression-induced inflammatory response was verified in lipopolysaccharide (LPS)-incubated glial cells . In contrast, over-expressing Rnf112 markedly attenuated ICH-induced brain injury by restraining inflammation via inactivating TLR-4/NF-κB pathway. In summary, our findings suggested that Rnf112 expression was highly involved in the progression of ICH, and targeting Rnf112 signaling might be a promising therapeutic strategy against ICH development.
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EXPERIMENTAL ANIMALS
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2024
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IF 2.2
Zhi-Hui GUAN,Di YANG,Yi WANG,Jia-Bin MA,Guo-Nian WANG
Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death. Ectodysplasin-A2 receptor (EDA2R) is a member of the TNF receptor family that has anti-inflammatory and antioxidant effects. However, to the best of our knowledge, its role in the progression of myocardial I/R injury remains unclear. The present study aimed to investigate the role of EDA2R during myocardial I/R injury and the molecular mechanisms involved. In vitro, dexmedetomidine (DEX) exhibited a protective effect on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and downregulated EDA2R expression. Subsequently, EDA2R silencing enhanced cell viability and reduced the apoptosis of cardiomyocytes. Furthermore, knockdown of EDA2R led to an elevated mitochondrial membrane potential (MMP), repressed the release of Cytochrome C and upregulated Bcl-2 expression. EDA2R knockdown also resulted in downregulated expression of Bax, and decreased activity of Caspase-3 and Caspase-9 in cardiomyocytes, reversing the effects of H/R on mitochondria-mediated apoptosis. In addition, knockdown of EDA2R suppressed H/R-induced oxidative stress. Mechanistically, EDA2R knockdown inactivated the NF-κB signaling pathway. Additionally, downregulation of EDA2R weakened myocardial I/R injury in mice, as reflected by improved left ventricular function and reduced infarct size, as well as suppressed apoptosis and oxidative stress. Additionally, EDA2R knockdown repressed the activation of NF-κB signal in vivo. Collectively, knockdown of EDA2R exerted anti-apoptotic and antioxidant effects against I/R injury in vivo and in vitro by suppressing the NF-κB signaling pathway.
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