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Toll-Like Receptor 2 Antagonist Ameliorates Type 2 Diabetes Mellitus Associated Neuropathic Pain by Repolarizing Pro-inflammatory Macrophages

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Abstract

Diabetic neuropathy is one of the common complications of type 2 diabetes mellitus (T2DM) with severe outcomes. The mechanisms of physiopathology of diabetic neuropathy are not well elucidated. Inflammation and inflammatory macrophages are recognized to be crucial in diabetic neuropathy. Toll-like receptor 2 (TLR2) is an important factor in innate immune response which could promote the polarization of inflammatory macrophages. In present study, we evaluated the effects of a TLR2 antagonist CU-CPT22 on diabetic neuropathy. We induced T2DM in mice by feeding with high fat diet (HFD). We measured the body weight, blood glucose level, paw withdrawal threshold, inflammatory cytokine production, and macrophages infiltration in T2DM mice. We evaluated the effects of CU-CPT22 on pro-inflammatory cytokines production, macrophage marker expression in lipopolysaccharides (LPS)-treated BMDMs. We administrated CU-CPT22 in T2DM mice and measured the pro-inflammatory cytokines levels, expression of macrophages markers in sciatic nerve (SCN), and paw withdrawal threshold. T2DM mice had significantly increased body weight and blood glucose, and had significantly decreased paw withdrawal threshold. Obvious increased pro-inflammatory cytokine level and infiltration of M1 phenotype macrophages was observed in SCN from T2DM mice. CU-CPT22 prevented pro-inflammatory cytokine production in LPS-treated BMDMs and re-polarized them to M2 phenotype. CU-CPT22 suppressed the inflammation and induced M2 macrophages in SCN from T2DM mice, and ameliorated the paw withdrawal threshold in T2DM mice. CU-CPT22 ameliorates neuropathic pain in T2DM by promoting M2 phenotype macrophages.

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Acknowledgements

The study was supported by Medical Science Research Project of Hebei Province (20191458).

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Authors and Affiliations

  1. Department of Neurosurgery, the First Hospital of Shijiazhuang, Shijiazhuang, China

    Jun Tian

  2. Department of Anesthesiology, the First Hospital of Shijiazhuang, Shijiazhuang, China

    Tieying Song, Hong Wang & Xiaojing Ma

  3. Department of Gynaecology, Maternal and Child Health Care Hospital of Shijiazhuang, Shijiazhuang, China

    Wenli Wang

  4. Department of Gynecology, Shijiazhuang First Hospital, Shijiazhuang, China

    Yue Hu

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  1. Jun Tian
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Correspondence to Tieying Song.

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Tian, J., Song, T., Wang, H. et al. Toll-Like Receptor 2 Antagonist Ameliorates Type 2 Diabetes Mellitus Associated Neuropathic Pain by Repolarizing Pro-inflammatory Macrophages. Neurochem Res 46, 2276–2284 (2021). https://doi.org/10.1007/s11064-021-03365-3

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  • DOI: https://doi.org/10.1007/s11064-021-03365-3

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