Toll-like receptor activity in patients with obstructive sleep apnea

Akinnusi, Morohunfolu E.; Jaoude, Philippe; Kufel, Thomas J.; El-Solh, Ali

doi:10.1007/s11325-012-0791-2

Cited by 44 publications

(36 citation statements)

References 44 publications

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“…In the present study, we found that both TLR2/6 co-expression and TLR2 expression on monocyte were increased either in SDB patients with low Min SaO 2 or with IHR treatment in vitro. In accordance with our results, enhanced expression and downstream signaling events of TLR2 and TLR4 were demonstrated in circulating monocytes from OSA patients and reversed with CPAP treatment in a recent study [31]. High TLR2 expression level on monocytes has been reported to be an independent risk factor associated with atherogenesis [32].…”

Section: Discussionsupporting

confidence: 92%

Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in patients with obstructive sleep apnea

Chen

Liou

et al. 2015

Sleep Breath

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Section: Discussionsupporting

confidence: 92%

Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in patients with obstructive sleep apnea

Chen

Liou

et al. 2015

Sleep Breath

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“…Monocytes isolated from OSA patients have elevated TLR2 and TLR4 expression (Akinnusi et al . ), suggesting increased pro‐inflammatory responses in these cells. In agreement, TLR2, TLR4 and pro‐inflammatory cytokine expression in OSA patients are normalized by Continuous Positive Airway Pressure (CPAP), suggesting a causal role for CIH and/or sleep fractionation (Akinnusi et al .…”

Section: Introductionmentioning

confidence: 98%

Mechanisms of microglial activation in models of inflammation and hypoxia: Implications for chronic intermittent hypoxia

Kiernan

Smith

Mitchell

et al. 2016

The Journal of Physiology

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Chronic intermittent hypoxia (CIH) is a hallmark of sleep apnoea, a condition associated with diverse clinical disorders. CIH and sleep apnoea are characterized by increased reactive oxygen species formation, peripheral and CNS inflammation, neuronal death and neurocognitive deficits. Few studies have examined the role of microglia, the resident CNS immune cells, in models of CIH. Thus, little is known concerning their direct contributions to neuropathology or the cellular mechanisms regulating their activities during or following pathological CIH. In this review, we identify gaps in knowledge regarding CIH-induced microglial activation, and propose mechanisms based on data from related models of hypoxia and/or hypoxia-reoxygenation. CIH Abstract figure legend Putative mechanisms whereby CIH may contribute to CNS inflammation. Schematic diagram depicting three independent, but interacting, mechanisms of CIH-induced inflammation and neuropathology, and potential interactions between them. CIH increases reactive oxygen species with subsequent peripheral inflammation (1), neuronal injury (2) and microglial activation (3). Peripheral inflammation can cause CNS inflammation via diffusion of inflammatory molecules across an intact or compromised blood-brain barrier (BBB), and/or via vagal afferent neuron activation leading to secondary inflammation in the CNS, and pro-inflammatory microglial activities (A). Peripheral inflammation can induce neuronal injury or cell death by similar mechanisms (B), and/or by microglial production of pro-inflammatory or neurotoxic molecules (C). Neuron-microglial communication propagates neuroinflammation with damaged neurons or glia releasing damage-associated molecular patterns (DAMPs) into the extracellular space where they elicit microglial inflammatory activities via activation of pattern recognition receptors (e.g. Toll-like receptors) or scavenger receptors (D).

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“…Toll-like receptor 4 (TLR4), a typical representative of pattern recognition receptors in innate immune responses, plays an important role in activation of inflammation in atherosclerosis. It has been recently demonstrated that IHR accelerated growth and vulnerability of atherosclerotic plaque, which probably acted by triggering the activation of TLR4/NF-κB signaling [4][5][6][7]. Acting as both up-stream and down-stream mediators of TLR signaling, tumor necrosis factor (TNF)-α has been shown to be upregulated in OSA patients, and this increase became more pronounced with the more severe grades of OSAS, indicating that TNF-α might be a promising circulating biomarker for the development of OSA [8].…”

Section: Introductionmentioning

confidence: 99%

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

Chen

Hsu

et al. 2020

IJMS

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The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

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Toll-like receptor activity in patients with obstructive sleep apnea

Cited by 44 publications

References 44 publications

Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in patients with obstructive sleep apnea

Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in patients with obstructive sleep apnea

Mechanisms of microglial activation in models of inflammation and hypoxia: Implications for chronic intermittent hypoxia

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

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