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

Chen, Yung‐Che; Su, Mu-Chun; Liou, Chia‐Wei; Liu, Shih-Feng; Chen, Chung‐Jen; Lin, Hsin‐Ching; Hsiao, Chang‐Chun; Wang, Ting‐Ya; Wang, Chin‐Chou; Chin, Chien-Hung; Huang, Kuo‐Tung; Lin, An‐Shen

doi:10.1007/s11325-014-1116-4

Cited by 19 publications

(15 citation statements)

References 36 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Patients with OSA show a rapid decrease in serum and plasma BDNF levels during initiation of the treatment (with PAPdevice), likely reflecting enhanced neuronal demand for BDNF in this condition. (40) Similarly, OSA patients had increased TLR2-expressions on blood immune cells, which could be reversed with PAP treatment (41). TLR2-deficiency has been shown to impair neurogenesis previously (42) and more recently, the TLR2-receptor has been shown to enhance adult neurogenesis in the hippocampal DG after cerebral ischaemia (43).…”

Section: Discussionmentioning

confidence: 98%

The Innate Immune Toll-Like Receptor-2 modulates the Depressogenic and Anorexiolytic Neuroinflammatory Response in Obstructive Sleep Apnoea

Polšek

Cash

Veronese³

et al. 2019

Preprint

View full text Add to dashboard Cite

243/250) Background:The neurological mechanisms of the disease process of obstructive sleep apnea, the second most frequent sleep disorder, remain unclear whilst its links with several major neuropsychiatric disorders, such as depression, anxiety and even Alzheimer's disorder, are increasingly recognised. A radical theory, that inflammation in the brain may underlie certain phenotypes of many of these disorders, has been proposed, and the microglial TLR2 system may serve as an important crossroad at the borderlands of several pathogenesis. This study undertook to investigate whether a neuroinflammatory response occurs under conditions of OSA, and whether it might be related to a modulated response due to TLR2 functionality in an established rodent model of OSA. Methods:The effects of three weeks' exposure to chronic intermittent hypoxia were monitored in mice with or without functional TLR2 (C57BL/6-Tyrc-Brd-Tg(Tlr2-luc/gfp)Kri/Gaj; TLR2 -/-, C57BL/6-Tlr2tm1Kir), that were investigated by multimodal in vivo and ex vivo imaging, combining magnetic resonance and bioluminescence imaging and a variety of functional tests. Results:An acute neuroinflammatory response was demonstrated following the three days in the basal forebrain of mice, and more chronically in other parts of the frontal cortex. Adaptive changes in specific neurocircuitry were demonstrated, with significant links to agitated (mal)adaptive behaviour under episodes of stress, and an increased ability to gain weight. Conclusions:Our results suggest that microglial activation and an innate immune response might be the missing link underlying the pathogenesis of well known structural, psychologic and metabolic changes experienced by some patients with OSA.

show abstract

“…PMBC from six healthy subjects (600 μL per well, and adjusted to 1×10 6 cells per ml) were exposed to normoxia (NOX) or IHR in a custom-designed, incubation chambers which are attached to an external O2-CO2-N2 computer-driven controller, as described previously[12]. Air-phase set point consisted of a 35-min hypoxic period (0% O2 and 5% CO2), followed by 25 min of re-oxygenation (21% O2 and 5% CO2), using the BioSpherix OxyCycler C42 system (BioSpherix, Redfield, NY), 7 hours each day for 4 days.…”

Section: Methodsmentioning

confidence: 99%

Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea

Chen

et al. 2017

PLoS ONE

Self Cite

View full text Add to dashboard Cite

We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients on long-term continuous positive airway pressure treatment (VSOC). Comparisons of the microarray gene expression data identified eight genes up-regulated with OSA and down-regulated with CPAP treatment, and five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein expression levels of two genes related to endothelial tight junction (AMOT P130, and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1 P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was increased in OSA patients with excessive daytime sleepiness, BIRC3 protein expression was decreased in OSA patients with hypertension, and LGALS3 protein expression was increased in OSA patients with chronic kidney disease. In vitro short-term intermittent hypoxia with re-oxygenation experiment showed immediate over-expression of ADAR1 P150. In conclusion, we identified a novel association between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index in OSA patients. AMOT and GALIG may constitute an important determinant for the development of hypersomnia and kidney injury, respectively, while BIRC3 may play a protective role in the development of hypertension.

show abstract

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

Abstract: OSA patients had increased TLR2/6 co-expressions on blood immune cells, which were related to their immune cell counts and could be reversed with CPAP treatment. In vitro IHR could induce TLR2/6 co-upregulation.

Cited by 19 publications

References 36 publications

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

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

The Innate Immune Toll-Like Receptor-2 modulates the Depressogenic and Anorexiolytic Neuroinflammatory Response in Obstructive Sleep Apnoea

Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea

Contact Info

Product

Resources

About