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miR-146a-5p Antagonized AGEs- and P.g-LPS-Induced ABCA1 and ABCG1 Dysregulation in Macrophages via IRAK-1 Downregulation

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Abstract

The miR-146-mediated IL-1 receptor-associated kinase 1 (IRAK-1) feedback circuit has been shown to inhibit inflammatory response in macrophages against lipopolysaccharide (LPS). The aim of this study is to compare the antagonized effects of miR-146a-5p on Porphyromonas gingivalis (P.g) lipolysaccharide (LPS)- and advanced glycation end products (AGEs)-triggered ABCA1 and ABCG1 dysregulation and explore the underlying mechanism. THP-1-derived macrophages transfected with miRNA mimics or not were treated with P.g LPS or AGE-BSA, respectively. The mechanism of endotoxin tolerance was mimicked. miR-146a-5p levels and protein levels of IRAK-1, LXRα/β, ABCA1, and ABCG1 were detected by stem–loop reverse transcription followed by TaqMan PCR analysis and Western blotting. Our results showed that miR-146a-5p levels were significantly increased in macrophages after 24 h of stimulation with high dose of P.g LPS or AGE-BSA. Macrophages transfected with miR-146a-5p mimics attenuated the dysregulation of ABCA1/G1 induced by P.g LPS and AGEs through IRAK-1 downregulation. In low-dose LPS-tolerized cells, elevated miR-146a-5p antagonized the increase of ABCA1, ABCG1, and IRAK-1. However, low-dose AGE-BSA did not increase miR-146a-5p levels. In conclusion, the model of endotoxin tolerance is suitable for the antagonistic effects on the dysregulation of ABCA1/G1 induced by high dose of P.g LPS. Conversely, low-dose AGEs did not induce the model of P.g LPS-mediated tolerance.

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Acknowledgments

This work was supported by grants from the Medical Research Foundation of the Health Planning Commission of Hebei Province of China (No. 20130315) and the Scientific Research Program for Returned Scholars, Department of Human Resources and Social Security of Hebei Province of China.

Competing Interests

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Internal Medicine, Hebei Medical University, No.361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, People’s Republic of China

    Xia Li, Jia Liu & Xiao-Ming Shang

  2. Department of Cardiovasology, Tangshan Gongren Hospital affiliated to Hebei Medical University, Tangshan, Hebei, 063000, People’s Republic of China

    Zheng Ji, Si Li, Ya-Nan Sun & Xiao-Ming Shang

  3. Department of Clinical Laboratory Center, Tangshan Gongren Hospital, No.27 Wenhua Road, Tangshan, Hebei, 063000, People’s Republic of China

    Ying Liu, Wei Tian & Yun-Tao Zhou

  4. Tangshan Key Laboratory of Clinical Molecule Diagnosis and Treatment, Tangshan Gongren Hospital, No. 27 Wenhua Road, Tangshan, Hebei, 063000, People’s Republic of China

    Ying Liu, Wei Tian & Yun-Tao Zhou

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  1. Xia Li
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  3. Si Li
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  6. Ying Liu
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  7. Wei Tian
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  8. Yun-Tao Zhou
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  9. Xiao-Ming Shang
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Correspondence to Yun-Tao Zhou or Xiao-Ming Shang.

Additional information

Zheng Ji holds a MD, Tangshan Gongren Hospital.

Wei Tian holds a PhD, Tangshan Gongren Hospital.

Yun-Tao Zhou holds a PhD, Tangshan Gongren Hospital.

Xiao-Ming Shang holds a MD, Hebei Medical University, Tangshan Gongren Hospital affiliated to Hebei Medical University.

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Li, X., Ji, Z., Li, S. et al. miR-146a-5p Antagonized AGEs- and P.g-LPS-Induced ABCA1 and ABCG1 Dysregulation in Macrophages via IRAK-1 Downregulation. Inflammation 38, 1761–1768 (2015). https://doi.org/10.1007/s10753-015-0153-x

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  • DOI: https://doi.org/10.1007/s10753-015-0153-x

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