Involvement of the p38 MAPK signaling pathway in overexpression of matrix metalloproteinase-9 during the course of brain edema in 1,2-dichloroethane-intoxicated mice

Jin, Xinqiao; Liao, Yingjun; Tan, Xiaoqiong; Guo, Jingjing; Wang, Gaoyang; Zhao, Fenghong; Jin, Yaping

doi:10.1016/j.neuro.2018.07.022

Cited by 9 publications

(10 citation statements)

References 39 publications

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“…Consistent with our previous studies [6,7], MMP-9 was overexpressed and BBB was disrupted during the course of 1,2-DCE-induced brain edema in mice. Moreover, we further demonstrated that MMP-9 overexpression and BBB disruption during the course of 1,2-DCE-induced brain edema were mediated through the p38 MAPK/NF-κB signaling pathway.…”

Section: Resultssupporting

confidence: 92%

“…In previous studies, we found that matrix metalloproteinase-9 (MMP-9) was upregulated transcriptionally during the formation of brain edema that was induced by subacute poisoning of 1,2-DCE in mice. We also found that the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway was activated and involved in the overexpression of MMP-9 [6,7]. Studies thus far have demonstrated that MMP-9 is substantially overexpressed in many brain diseases, which acts as not only a proteolytic enzyme involved in the disruption of the blood–brain barrier (BBB), but also an inflammatory mediator playing an important role in neuroinflammation [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

“…Although we have found that NF-κB could be activated through p38 MAPK signaling pathway during the course of 1,2-DCE-induced brain edema in mice [6], it is still unknown whether activation of NF-κB could enhance MMP-9 expression and whether BBB integrity might be disrupted by excessive MMP-9. Thus, in the present study, we further hypothesized that the p38 MAPK/NF-κB signaling pathway might be involved in the activation of glial cells and as a consequence, the production of the proinflammatory factor IL-1β and the inflammatory mediators that induce neuroinflammation lead to BBB disruption and brain edema formation in 1,2-DCE-intoxicated mice.…”

Section: Introductionmentioning

confidence: 99%

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Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema

Jin

Wang

Liao

et al. 2019

Cells

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We previously reported that expression of matrix metalloproteinase-9 (MMP-9) mRNA and protein was upregulated during 1,2-dichloroethane (1,2-DCE) induced brain edema in mice. We also found that the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway resulted in MMP-9 overexpression and nuclear factor-κB (NF-κB) activation in mice treated with 1,2-DCE. In this study, we further hypothesized that inflammatory reactions mediated by the p38 MAPK/ NF-κB signaling pathway might be involved in MMP-9 overexpression, blood–brain barrier (BBB) disruption and edema formation in the brain of 1,2-DCE-intoxicated mice. Our results revealed that subacute poisoning by 1,2-DCE upregulates protein levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and p-p65 in mouse brains. Pretreatment with an inhibitor against p38 MAPK attenuates these changes. Moreover, pretreatment with an inhibitor against NF-κB attenuates alterations in brain water content, pathological indications notable in brain edema, as well as mRNA and protein expression on levels of MMP-9, VCAM-1, ICAM-1, iNOS, and IL-1β, tight junction proteins (TJs), GFAP and Iba-1 in the brain of 1,2-DCE-intoxicated mice. Furthermore, pretreatment with an inhibitor against MMP-9 obstructs the decrease of TJs in the brain of 1,2-DCE-intoxicated mice. Lastly, pretreatment with an antagonist against the IL-1β receptor also attenuates changes in protein levels of p-p38 MAPK, p-p65, p-IκB, VCAM -1, ICAM-1, IL-1β, and Iba-1 in the brain of 1,2-DCE-intoxicated-mice. Taken together, findings from the current study indicate that the p38 MAPK/ NF-κB signaling pathway might be involved in the activation of glial cells, and the overproduction of proinflammatory factors, which might induce inflammatory reactions in the brain of 1,2-DCE-intoxicated mice that leads to brain edema.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema

Jin

Wang

Liao

et al. 2019

Cells

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“…cDNA was obtained using the RevertAid First Strand cDNA Synthesis Kit (Thermo Fisher Scientific). The following primers were used: TLR-4, sense 5′-GCAATG TCTGGCAGGTGTA-3′ and antisense 5′-CAAGGG ATAAGAACGCTGAGA-3′ [33]; MD-2, sense 5′-ATGTTGCCATTTATTCTCTTTTCGACG-3′ and antisense 5′-ATTGACATCACGGCGCTGAATGATG-3′ [34]; CD-14, sense 5′-CGTCTAGAAGAACACCAT CGCTGTAAAG-3′ and antisense 5′-CGTCTAGAAG AACACCATCGCTGTAAAG-3′ [35]; TNF, sense 5′-TTCTGTCTACTGAACTTCGGGGTGATCGGTCC-3′ and antisense 5′-GTATGAGATAGCAAATCGGCTG ACGGTGTGGG-3′ [36]; GAPDH, sense 5′-TGAAGG TCGGTGTGAACGGATTTGGC-3′ and antisense 5′-CATGTAGGCCATGAGGTCCACCAC-3′ [37]; c-fos, sense 5′-CGGGTTTCAACGCCGACTA-3′ and antisense 5′-TGGCACTAGAGACGGACAGAT-3′ [38]; IL-10, sense 5′-ATGCAGGACTTTAAGGGTTACTTGGG TT-3′ and antisense 5′-ATTTCGGAGAGAGGTACA AACGAGGTTT-3′; TGFβ, sense 5′-CGCAACAACG CCATCTATGAGAAA-3′ and antisense 5′-TTGCAG GAGCGCACAATCATGTTG-3′ [39]. PCR products were resolved on 2% agarose gels and stained with ethidium bromide.…”

Section: Rna Extraction and Rt-pcrmentioning

confidence: 99%

Mutant Huntingtin affects toll-like receptor 4 intracellular trafficking and cytokine production in mast cells

Pérez-Rodríguez

Ibarra-Sánchez

Román-Figueroa

et al. 2020

J Neuroinflammation

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Background: Huntington's disease (HD) is caused by the expression of a mutated variant of Huntingtin (mHtt), which results in the complex pathology characterized by a defective function of the nervous system and altered inflammatory responses. While the neuronal effects of mHtt expression have been extensively studied, its effects on the physiology of immune cells have not been fully described. Mast cells (MCs) are unique tissue-resident immune cells whose activation has been linked to protective responses against parasites and bacteria, but also to deleterious inflammatory allergic reactions and, recently, to neurodegenerative diseases. Methods: Bone marrow-derived mast cells (BMMCs) were obtained from wild-type (WT-) and mHtt-expressing (R6/ 1) mice to evaluate the main activation parameters triggered by the high-affinity IgE receptor (FcεRI) and the Tolllike receptor (TLR) 4. Degranulation was assessed by measuring the secretion of β-hexosaminidase, MAP kinase activation was detected by Western blot, and cytokine production was determined by RT-PCR and ELISA. TLR-4 receptor and Htt vesicular trafficking was analyzed by confocal microscopy. In vivo, MC-deficient mice (c-Kit Wsh/Wsh) were intraperitonally reconstituted with WT or R6/1 BMMCs and the TLR4-induced production of the tumor necrosis factor (TNF) was determined by ELISA. A survival curve of mice treated with a sub-lethal dose of bacterial lipopolysaccharide (LPS) was constructed. Results: R6/1 BMMCs showed normal β-hexosaminidase release levels in response to FcεRI, but lower cytokine production upon LPS stimulus. Impaired TLR4-induced TNF production was associated to the lack of intracellular dynamin-dependent TLR-4 receptor trafficking to perinuclear regions in BMMCs, a diminished ERK1/2 and ELK-1 phosphorylation, and a decrease in c-fos and TNF mRNA accumulation. R6/1 BMMCs also failed to produce TLR4induced anti-inflammatory cytokines (like IL-10 and TGF-β). The detected defects were also observed in vivo, in a MCs-dependent model of endotoxemia. R6/1 and c-Kit Wsh/Wsh mice reconstituted with R6/1 BMMCs showed a decreased TLR4-induced TNF production and lower survival rates to LPS challenge than WT mice.

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“…Such kinase can be activated by various environmental stresses and proinflammatory cytokines [27]. Evidence confirmed that p38/MAPK plays a key role in the formation of cerebral edema [28,29]. MAPK14 is widely present in the brain tissue, hence raises the hypothesis that it can reflect the degree of change in brain tissue concentration by detecting its concentration in the blood.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of MAPK14 as a Potential Biomarker for Cardioembolic Stroke

Zhao

Wang

2020

BioMed Research International

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The aim of this study was to obtain the candidate genes and biomarkers that are significantly related to cardioembolic stroke (CS) by applying bioinformatics analysis. In accordance with the results of the weighted gene coexpression network analysis (WGCNA) in the GSE58294 dataset, 11 CS-related coexpression network modules were identified in this study. Correlation analysis showed that the black and pink modules are significantly associated with CS. A total of 18 core genes in the black module and one core gene in the pink module were determined. We then identified differentially expressed genes (DEGs) of CS at 3 h, 5 h, and 24 h postonset. After performing intersection, it was found that 311 genes were coexpressed at these three time points. These genes were majorly enriched in positive regulation of transferase activity and regulation of peptidase activity. The abovementioned coexpressed DEGs were subjected to protein-protein interaction analysis and subnetwork module analysis. Subsequently, we used cytoHubba to obtain 11 key genes from DEGs. The intersection of the core genes screened from WGCNA and the key genes selected from DEGs yielded the MAPK14 gene. The expression level of MAPK14 on the receiver operating characteristic (ROC) curves of CS at 3 h, 5 h, and 24 h showed that the area under the ROC curve (AUC) was 0.923, 0.934, and 0.941, respectively. In a nutshell, MAPK14 screened out by using WGCNA showed differential expression in CS. We conclude that MAPK14 can be used as a potential biological marker of CS and exhibits potential to predict the physiopathological condition of CS patients.

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Involvement of the p38 MAPK signaling pathway in overexpression of matrix metalloproteinase-9 during the course of brain edema in 1,2-dichloroethane-intoxicated mice

Cited by 9 publications

References 39 publications

Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema

Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema

Mutant Huntingtin affects toll-like receptor 4 intracellular trafficking and cytokine production in mast cells

Integrative Analysis of MAPK14 as a Potential Biomarker for Cardioembolic Stroke

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