Upregulated Expression of Toll-like Receptor 4 in Peripheral Blood of Ischaemic Stroke Patients Correlates with Cyclooxygenase 2 Expression

Ferronato, Silvia; Gomez-Lira, Macarena; Olivato, Silvia; Scuro, Alberto; Veraldi, Gian Franco; Romanelli, Maria; Patuzzo, Cristina; Malerba, Giovanni; Pignatti, Pierfranco; Mazzucco, Sara

doi:10.1016/j.ejvs.2010.11.019

Cited by 20 publications

(19 citation statements)

References 25 publications

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“…Most NSAIDs inhibit the activity of cyclooxygenase (COX)-1 and −2, and downstream synthesis of prostaglandins. It has been observed that COX-2 is increased in the blood of ischemic stroke patients (Ferronato et al, 2011). Also in the case of NSAIDs most studied have been focused on neuroprotection and the acute and subacute phases of microglia-mediated events.…”

Section: Other Pharmacological Modulations Of Inflammatory Signalimentioning

confidence: 99%

Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors

Anttila

Whitaker

Wires

et al. 2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Stroke is the leading cause of disability in adults. Drug treatments that target stroke-induced pathological mechanisms and promote recovery are desperately needed. In the brain, an ischemic event triggers major inflammatory responses that are mediated by the resident microglial cells. In this review, we focus on the microglia activation after ischemic brain injury as a target of immunomodulatory therapeutics. We divide the microglia-mediated events following ischemic stroke into three categories: acute, subacute, and long-term events. This division encompasses the spatial and temporal dynamics of microglia as they participate in the pathophysiological changes that contribute to the symptoms and sequela of a stroke. The importance of Toll-like receptor (TLR) signaling in the outcomes of these pathophysiological changes is highlighted. Increasing evidence shows that microglia have a complex role in stroke pathophysiology and they mediate both detrimental and beneficial effects on stroke outcome. So far, most of the pharmacological studies in experimental models of stroke have focused on neuroprotective strategies which are impractical for clinical applications. Post-ischemic inflammation is long lasting and thus, could provide a therapeutic target for novel delayed drug treatment. However, more studies are needed to elucidate the role of microglia in the recovery process from an ischemic stroke and to evaluate the therapeutic potential of modulating post-ischemic inflammation to promote functional recovery.

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Section: Other Pharmacological Modulations Of Inflammatory Signalimentioning

confidence: 99%

Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors

Anttila

Whitaker

Wires

et al. 2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…This leads to the degradation of inhibitor of kappa B (I κ B) and the triggering translocation of nuclear factor- κ B (NF- κ B) into the nucleus, which induces the production of proinflammatory cytokines such as interleukin-1 β (IL-1 β ), IL-6, and tumor necrosis factor- α (TNF- α ) [11]. Clinical studies have reported that the expression levels of TLR2 and TLR4 in peripheral blood in the acute stage are related to the severity and prognosis of patients in the following stage [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Paeonol Mediates Anti‐Inflammation via Suppressing Toll‐Like Receptor 2 and Toll‐Like Receptor 4 Signaling Pathways in Cerebral Ischemia‐Reperfusion Injured Rats

Liao

Tsai²,

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Paeonol is a phenolic compound derived from Paeonia suffruticosa Andrews (MC) and P. lactiflora Pall (PL). Paeonol can reduce cerebral infarction volume and improve neurological deficits through antioxidative and anti-inflammatory effects. However, the anti-inflammatory pathway of paeonol remains unclear. This study investigated the relationship between anti-inflammatory responses of paeonol and signaling pathways of TLR2 and TLR4 in cerebral infarct. We established the cerebral ischemia-reperfusion model in Sprague Dawley rats by occluding right middle cerebral artery for 60 min, followed by reperfusion for 24 h. The neurological deficit score was examined, and the brains of the rats were removed for cerebral infarction volume and immunohistochemistry (IHC) analysis. The infarction volume and neurological deficits were lower in the paeonol group (pretreatment with paeonol; 20 mg/kg i.p.) than in the control group (without paeonol treatment). The IHC analysis revealed that the number of TLR2-, TLR4-, Iba1-, NF-κB- (P50-), and IL-1β-immunoreactive cells and TUNEL-positive cells was significantly lower in the paeonol group; however, the number of TNF-α-immunoreactive cells did not differ between the paeonol and control groups. The paeonol reveals some neuroprotective effects in the model of ischemia, which could be due to the reduction of many proinflammatory receptors/mediators, although the mechanisms are not clear.

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“…11 Controls were individuals presenting no sign of atherosclerotic plaques at ecodoppler examination. DNA and total RNA were extracted from peripheral blood samples.…”

Section: Resultsmentioning

confidence: 99%

“…Clinical severity of stroke was rated through the National Institute of Health Stroke Scale (NIHSS). 12 Functional polymorphisms À1607T4C, À2026A4G and À2604G4A 13 were genotyped by PCR-restriction fragment length polymorphism (Supplementary Table 2), and gene expression was performed by Real-time PCR as described 11 (Supplementary Table 3). By in silico analysis, other single-nucleotide polymorphisms present in the region do not alter transcriptionbinding sites or are in strong linkage disequilibrium with the selected ones.…”

Section: Resultsmentioning

confidence: 99%

Polymorphism −2604G>A variants in TLR4 promoter are associated with different gene expression level in peripheral blood of atherosclerotic patients

et al. 2013

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Toll-like receptor-4 (TLR4) is a primary receptor of the innate immune reaction and compelling evidence demonstrates its involvement in the pathogenesis of atherosclerosis and stroke. TLR4 is constitutively expressed on monocytes and endothelial cells; it is highly expressed in atherosclerotic plaques and in peripheral blood of patients after ischemic stroke. Polymorphisms in the promoter region that alter the transcriptional regulation of this gene may represent genetic risk factors involved in the predisposition to atherosclerotic disease. In this study we investigated the effect on TLR4 gene expression of three polymorphisms in the upstream regulatory region at positions -1607T>C/rs10759932, -2026A>G/rs1927914 and -2604G>A/rs10759931 in peripheral blood of atherosclerotic patients. RNA from individuals homozygous for the -2604A allele showed a lower expression of the gene when compared to patients carrying the counterparts GG+GA. Electrophoretic mobility shift assays showed differences in the electrophoretic mobility of the DNA-nuclear protein complexes formed by the G>A variants, suggesting that the two alleles differ in their binding affinity to transcriptional factors.

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Upregulated Expression of Toll-like Receptor 4 in Peripheral Blood of Ischaemic Stroke Patients Correlates with Cyclooxygenase 2 Expression

Abstract: Our results suggest that the peripheral mechanism of inflammatory injury after stroke may be mediated by TLR4 through a COX-2-dependent pathway.

Cited by 20 publications

References 25 publications

Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors

Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors

Neuroprotective Effect of Paeonol Mediates Anti‐Inflammation via Suppressing Toll‐Like Receptor 2 and Toll‐Like Receptor 4 Signaling Pathways in Cerebral Ischemia‐Reperfusion Injured Rats

Polymorphism −2604G>A variants in TLR4 promoter are associated with different gene expression level in peripheral blood of atherosclerotic patients

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