Salvianolic Acid B Ameliorates Cerebral Ischemia/Reperfusion Injury Through Inhibiting TLR4/MyD88 Signaling Pathway

Wang, Yujue; Chen, Guang; Yu, Xin; Li, Yunchao; Zhang, Li; He, Zongze; Zhang, Nannan; Yang, Xiuping; Zhao, Yansheng; Li, Na; Qiu, Hong

doi:10.1007/s10753-016-0384-5

Cited by 72 publications

(41 citation statements)

References 36 publications

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“…In cerebral ischemia/reperfusion models for stroke injury, HSP70 binds to TLR4, activating MyD88-IRAK-TRAF6 and NF-κB pathways, with downstream induction of TNFα and other cytokines [60, 61], as observed for nPM-LPS responses (Fig. 8).…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 in glial inflammatory responses to air pollution in vitro and in vivo

Woodward

Levine

Haghani

et al. 2017

J Neuroinflammation

116

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BackgroundExposure to traffic-related air pollution (TRAP) is associated with accelerated cognitive aging and higher dementia risk in human populations. Rodent brains respond to TRAP with activation of astrocytes and microglia, increased inflammatory cytokines, and neurite atrophy. A role for Toll-like receptor 4 (TLR4) was suggested in mouse TLR4-knockouts, which had attenuated lung macrophage responses to air pollution.MethodsTo further analyze these mechanisms, we examined mixed glial cultures (astrocytes and microglia) for RNA responses to nanoscale particulate matter (nPM; diameter <0.2 μm), a well-characterized nanoscale particulate matter subfraction of TRAP collected from a local freeway (Morgan et al. Environ Health Perspect 2011; 119,1003–1009, 2011). The nPM was compared with responses to the endotoxin lipopolysaccharide (LPS), a classic TLR4 ligand, using Affymetrix whole genome microarray in rats. Expression patterns were analyzed by significance analysis of microarrays (SAM) for fold change and by weighted gene co-expression network analysis (WGCNA) to identify modules of shared responses between nPM and LPS. Finally, we examined TLR4 activation in hippocampal tissue from mice chronically exposed to nPM.ResultsSAM and WGCNA analyses showed strong activation of TLR4 and NF-κB by both nPM and LPS. TLR4 siRNA attenuated TNFα and other inflammatory responses to nPM in vitro, via the MyD88-dependent pathway. In vivo, mice chronically exposed to nPM showed increased TLR4, MyD88, TNFα, and TNFR2 RNA, and decreased NF-κB and TRAF6 RNA TLR4 and NF-κB responses in the hippocampus.ConclusionsThese results show TLR4 activation is integral in brain inflammatory responses to air pollution, and warrant further study of TLR4 in accelerated cognitive aging by air pollution.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0858-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 in glial inflammatory responses to air pollution in vitro and in vivo

Woodward

Levine

Haghani

et al. 2017

J Neuroinflammation

116

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“…Similar to these studies, our findings validated that CM significantly enhanced the expression of TLR4 both in CIAKI rats and NRK-52E cells. Since activation of TLR4 was validated to be related to different kinds of injuries in various experimental models [45- 48], we investigated the role of TLR4 in CM-induced injuries. Increase in the number of apoptotic cells and production of ROS were observed after exposure of cells to CM.…”

Section: Discussionmentioning

confidence: 99%

Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury

Tan

Zheng

Huang

et al. 2017

Cell Physiol Biochem

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Background: Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. Methods: We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We used inhibitor of TLR4 and NLRP3-siRNA to further testify their role in CIAKI in NRK-52E cells. Results: Iopromide caused elevation of SCr, BUN and NGAL level, decrease of endogenous creatinine clearance, morphological injury and tubular apoptosis, enhanced IL-1β and IL-18 expression, and increased expression of S100A8/A9, TLR4 and NLRP3 inflammsome. In NRK-52E cells, iopromide caused enhanced apoptotic rates and ROS generation, which could be ameliorated by inhibitor of TLR4 and NLRP3-siRNA. Moreover, inhibition of TLR4 dampened NLRP3 expression. Conclusion: S100A8/A9-TLR4-NLRP3 inflammasome pathway represented a key mechanism of CI-AKI, which provided a potential therapeutic target.

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“…Because the TLR4 signalling pathway plays critical roles in cerebral I/RI [19], we then assessed whether the TLR4 signalling pathway mediates the secretion of inflammatory cytokines and whether the ALAP or/and IPC-mediated neuroprotective effects are partly due to blocking the TLR signalling pathway. Therefore, we next analysed the expression levels of HMGB1,TLR4, MyD88, IKB-α and NF-kB in all groups.…”

Section: Effects Of Alap and Ipc On The Inflammatory Signalling Pathwmentioning

confidence: 99%

Alpha-Lipoic Acid Preconditioning and Ischaemic Postconditioning Synergistically Protect Rats from Cerebral Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/ NF-κB Signaling Pathway

Zhang

Fan

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: A combination of alpha-lipoic acid preconditioning (ALAP) and ischaemic preconditioning (IPC) has not been tested in an in vivo rat cerebral ischaemia/reperfusion injury (I/RI) model, and the potential protective mechanisms have not been well elucidated. The aim of this study was to investigate the role of the TLR4/ MyD88/ NF-κB signaling pathway in the synergistically neuroprotective and anti-inflammatory effects of ALAP and IPC. Methods: One hundred and fifty male Sprague-Dawley rats, weighing 180-230 g, were randomly divided into the following 5 groups: 1) sham-operated control; 2) I/R; 3) I/R+ALAP; 4) I/R+IPC; 5) I/R+IPC+ALAP. After 2 h of reperfusion, the infarct size, neurological deficit scores, brain oedema, oxidative stress, and inflammatory and apoptotic biomarkers were assessed. In addition, reactive oxygen species (ROS) and cell apoptosis were detected by DHE staining and TUNEL staining, respectively. Results: Both ALAP and IPC treatment attenuated the I/RI-induced neuronal injury, reflected by reductions in the infarct size, neurological deficit scores, brain oedema, lactate dehydrogenase (LDH) release and the inflammatory response, as well as decreased HMGB1, TLR4, MyD88, p65, C-Caspase 3 and Bax expression and increased IKB-α, HO-1, SOD-2 and Bcl-2 expression compared to that in the I/R group. Furthermore, the combination of the two strategies had synergistic anti-inflammatory effects and antioxidant benefits, ultimately limiting neuronal apoptosis. Conclusion: The ‘cocktail’ strategy exhibited a significant neuroprotection against I/RI by attenuating neuroinflammation via inhibition of the TLR4/MyD88/NF-κB signaling pathway.

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Salvianolic Acid B Ameliorates Cerebral Ischemia/Reperfusion Injury Through Inhibiting TLR4/MyD88 Signaling Pathway

Cited by 72 publications

References 36 publications

Toll-like receptor 4 in glial inflammatory responses to air pollution in vitro and in vivo

Toll-like receptor 4 in glial inflammatory responses to air pollution in vitro and in vivo

Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury

Alpha-Lipoic Acid Preconditioning and Ischaemic Postconditioning Synergistically Protect Rats from Cerebral Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/ NF-κB Signaling Pathway

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