Paraquat modulates microglia M1/M2 polarization via activation of TLR4-mediated NF-κB signaling pathway

Huang, Min; Li, Yingying; K, Wu; Yan, Weiguang; Tian, Tian; Wang, Yifan; Yang, Huifang

doi:10.1016/j.cbi.2019.108743

Cited by 45 publications

(23 citation statements)

References 31 publications

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“…This suggests that the inflammatory signalling pathway was activated and involved in kidney damage, which is consistent with the results of Garibotto et al [9]. The activation of TLR4 can lead to the translocation of NF-kB (p65) to the nucleus, thereby resulting in the activation of downstream NLRP3 protein [10][11][12][13] and inducing the inflammatory response. Some specific microRNAs play a crucial role in the fibrosis process of tissues [14,15].…”

Section: Discussionsupporting

confidence: 88%

Hydroxysafflor yellow A improves diabetes-induced renal fibrosis

Chen

et al. 2020

Arch Med Sci

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Introduction: This study aimed to discuss the use of hydroxysafflor yellow A (HSYA) to improve renal fibrosis induced by diabetes and its relative mechanisms, as well as to evaluate the level of renal histopathology and fibrosis in different rat groups. Material and methods: Sprague-Dawley (SD) rats (n = 27) were divided into the normal control (NC), diabetes mellitus (DM), and HSYA groups. The miRNA-140-5p mRNA, blood glucose (BG), 24-h urine protein (UP), total cholesterol (TC), triglyceride (TG), total anti-oxidant capacity (T-AOC), malondialdehyde (MDA), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) were measured in different groups. Moreover, the relative protein expression was measured via immunohistochemistry (IHC) assay. In the in vitro cell experiment, we discussed the effects of miRNA-140-5p on renal fibrosis induced by diabetes. Toll-like receptor 4 (TLR4), nuclear factor kB (p65) (NF-kB(p65)), NOD-like receptor protein 3 (NLRP3), Notch2, and collagen IV (Col-IV) protein expression were evaluated using western blotting in the different cell groups. We evaluated the important protein expressions and NF-kB(p65) nuclear volume by cellular immunofluorescence. A correlation between miRNA-140-5p and TLR4 was found by dual-luciferase reporter assay. Results: In the in vivo study, HSYA improved diabetes-induced renal fibrosis. The severity of fibrosis significantly decreased after treatment with HSYA. In the HSYA group, the miRNA-140-5p mRNA, BG, 24-h UP, TC, TG, T-AOC, MDA, IL-6, and TNF-α significantly improved, as well as the TLR4, NF-kB(p65), NLRP3, Notch2, and Col-IV proteins. In the in vitro experiment, miRNA-140-5p was significantly decreased after treatment with HSYA in diabetes-induced renal fibrosis. Conclusions: HSYA improved diabetes-induced renal fibrosis by regulating miRNA-140-5p.

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Section: Discussionsupporting

confidence: 88%

Hydroxysafflor yellow A improves diabetes-induced renal fibrosis

Chen

et al. 2020

Arch Med Sci

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“…in addition, c-c motif chemokine ligand 2 (ccl2) generated by microglia was observed to recruit cd8 + γδ T cells to the ischemic brain, which was identified to be the primary factor aggravating brain infarction (32,33). in fact, besides ischemic stroke, M1 microglia activation occurs in multiple other neurological diseases; for example, in an RD1 mouse model of retinal degeneration, flow cytometry analysis revealed that the percentage of T-lymphocyte activation antigen cd86 (cd86) + M1 microglia was markedly increased in the rapid degeneration phase (34); paraquat stimulation was revealed to activate M1 microglia, which subsequently activated the toll-like receptor-4 (Tlr4)-mediated nF-κB signaling pathway and resulted in the release of proinflammatory cytokines (35); and the number of low affinity immunoglobulin gamma Fc region receptor iii-a/b (cd16/32) + M1 microglia was significantly increased in the brains of subarachnoid hemorrhage model mice through the activation of the myeloid differentiation primary response protein Myd88 (Myd88)/mitogen-activated protein kinase pathway, whereas decreasing the percentage of M1 microglia significantly improved the neurological deficits (36). other results from the literature have indicated that M1 microglia activation can also aggravate brain damage in other types of neurological disease (34)(35)(36).…”

Section: Microgliamentioning

confidence: 99%

Modulators of microglia activation and polarization in ischemic stroke (Review)

et al. 2020

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ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. as the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. in response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. it has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. in addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified. Contents 1. introduction 2. Microglia 3. Modulatory mechanisms of microglia polarization 4. autophagy 5. conclusions

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“…Microglia, the resident macrophages of the brain, constantly survey the microenvironment and produce factors that influence surrounding astrocytes and neurons (Huang et al, 2019). Microglia can polarize into either the classically activated M1 phenotype or the alternatively activated M2 phenotype (Zhang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

DHZCP Modulates Microglial M1/M2 Polarization via the p38 and TLR4/NF-κB Signaling Pathways in LPS-Stimulated Microglial Cells

et al. 2020

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Intracerebral hemorrhage (ICH) is a disease with a significantly high rate of morbidity, mortality and disability. Inhibition of inflammation is considered a potential strategy for improving the clinical symptoms induced by ICH. The hallmark of neuroinflammation is microglial activation. Microglia can polarize into either the classically activated M1 (proinflammatory) phenotype, exacerbating neuronal damage, or the alternatively activated M2 (antiinflammatory) phenotype, exerting neuroprotection and promoting neuronal recovery. Promoting microglial polarization to the M2 phenotype may be a viable strategy for treating neuroinflammation. Several studies have indicated that promoting blood circulation and removing blood stasis exhibits therapeutic effects on intracerebral hemorrhage. Dahuang Zhechong Pill (DHZCP), a classical recipe that promotes blood circulation and removes blood stasis, has been reported to improve the clinical outcome of ICH. DHZCP has been shown to exert antiinflammatory effects. However, the detailed antiinflammatory mechanism of DHZCP in ICH has rarely been investigated. In this study, DHZCP inhibited lipopolysaccharide (LPS)-induced M1 microglial activation. DHZCP exerted antiinflammatory effects, by inhibiting LPS-induced M1 proinflammatory cytokine (TNF-a and IL-6), and iNOS production and increasing M2 antiinflammatory cytokine (IL-10) production. DHZCP also switched microglial polarization from M1 to M2, as indicated by significantly increased expression of M2 polarization markers (CD209, and CD206) and markedly decreased expression of an M1 polarization marker (CD54). In addition, DHZCP inhibited p38 and TLR4/NF-kB signaling activation, as demonstrated by inhibition of LPS-induced increases in p-p38, TLR4 and nuclear factor kappa B p-65 (NF-kB p-65) protein expression. Taken together, DHZCP modulates microglial M1/M2 polarization via the p38 and TLR4/NF-kB signaling pathways to confer antiinflammatory effects.

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Paraquat modulates microglia M1/M2 polarization via activation of TLR4-mediated NF-κB signaling pathway

Cited by 45 publications

References 31 publications

Hydroxysafflor yellow A improves diabetes-induced renal fibrosis

Hydroxysafflor yellow A improves diabetes-induced renal fibrosis

Modulators of microglia activation and polarization in ischemic stroke (Review)

DHZCP Modulates Microglial M1/M2 Polarization via the p38 and TLR4/NF-κB Signaling Pathways in LPS-Stimulated Microglial Cells

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