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

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Abstract

Purpose

Toll-like receptor (TLR) 2 can heterodimerise with TLR6 to detect diacylated lipoproteins. Hypoxia inducible factor-1 α co-ordinates selective induction of TLR2 and TLR6 during persistent hypoxia. We hypothesized that TLR 2/6 co-expression may be upregulated by chronic intermittent hypoxia with re-oxygenation (IHR) in obstructive sleep apnea (OSA).

Methods

TLR2/6 expressions on blood immune cells were measured in 144 patients with sleep-disordered breathing (SDB), including primary snoring (PS, n = 24), moderate to severe OSA (MSO, n = 60), very severe OSA (VSO, n = 36), and very severe OSA on continuous positive airway pressure (CPAP) treatment (VSOC, n = 24). An in vitro IHR experiment was also undertaken.

Results

Patients in both the MSO and VSO groups had increased TLR2/6 co-expression on CD16+ neutrophil than those in the PS group. Patients in the VSOC group had reduced TLR2/6 co-expression on neutrophil than those in either the MSO or VSO group. Blood absolute neutrophil count was positively but weakly correlated with TLR2/6 co-expression on neutrophil. TLR2/6 co-expressions on both CD14+ monocyte and CD3+CD4+T helper cell, and TLR2 expressions on both monocyte and T helper cell in SDB patients with low Minimum SaO2 (≦70 %) were all higher than those with high Minimum SaO2. In vitro IHR for 1–4 days resulted in TLR2/6 co-upregulation on both neutrophil and monocyte.

Conclusions

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.

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Acknowledgments

The authors acknowledge the technical support provided by the Genomic and Proteomic Core Laboratory, and Internal Medicine Core Facility of the Kaohsiung Chang Gung Memorial Hospital. The authors wish to thank Ms. Shu-Jun Kong, Ms. Lian-Rong Liu, and Mr. Wei-Zhe Liu for manual scoring of all PSG. This work was supported by grants (NMRPG8B6191 to M.C. Lin and NMRPG8A0241 to Y.C. Chen) from the National Science Council, Taiwan, and by a grant from the Chang Gung Memorial Hospital (CMRPG8A0981 to M.C. Lin), Taiwan.

Competing interests

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Yung-Che Chen, Mao-Chang Su, Shih-Feng Liu, Ting-Ya Wang, Chin-Chou Wang, Chien-Hung Chin, Kuo-Tung Huang, An-Shen Lin & Meng-Chih Lin

  2. Sleep Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Yung-Che Chen, Mao-Chang Su, Hsin-Ching Lin, Chin-Chou Wang, Chien-Hung Chin & Meng-Chih Lin

  3. Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Chia-Wei Liou

  4. Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Shih-Feng Liu

  5. Division of Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Chung-Jen Chen

  6. Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Hsin-Ching Lin

  7. Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan

    Yung-Che Chen, Chang-Chun Hsiao & Meng-Chih Lin

  8. Department of Respiratory Care, Chang Gung University of Science and Technology, Chia-yi, Taiwan

    Mao-Chang Su & Chin-Chou Wang

  9. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-Pei Rd, Niao-Sung District, Kaohsiung, Taiwan

    Meng-Chih Lin

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  1. Yung-Che Chen
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Correspondence to Meng-Chih Lin.

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Chen, YC., Su, MC., Liou, CW. et al. Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in patients with obstructive sleep apnea. Sleep Breath 19, 873–882 (2015). https://doi.org/10.1007/s11325-014-1116-4

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  • DOI: https://doi.org/10.1007/s11325-014-1116-4

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