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Ox-LDL Upregulates IL-6 Expression by Enhancing NF-κB in an IGF2-Dependent Manner in THP-1 Macrophages

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Abstract

Interleukin 6 (IL-6) is a pro-inflammatory cytokine that is well established as a vital factor in determining the risk of coronary heart disease and pathogenesis of atherosclerosis. Moreover, accumulating evidences have shown that oxidized low-density lipoprotein (ox-LDL) can promote IL-6 expression in macrophages. Nevertheless, the underlying mechanism of how ox-LDL upregulates IL-6 expression remains largely unexplained. We found that the expression of insulin-like growth factor 2 (IGF2), nuclear factor kappa B (NF-κB), and IL-6 was upregulated at both the messenger RNA (mRNA) and protein levels in a dose-dependent manner when treated with 0, 25, 50, or 100 μg/mL of ox-LDL for 48 h in THP-1 macrophages. Moreover, overexpression of IGF2 significantly upregulated NF-κB and IL-6 expressions in THP-1 macrophages. However, the upregulation of NF-κB and IL-6 expressions induced by ox-LDL were significantly abolished by IGF2 small interfering RNA (siRNA) in THP-1 macrophages. Further studies indicated the upregulation of IL-6 induced by ox-LDL could be abolished when treated with NF-κB siRNA in THP-1 macrophages. Ox-LDL might upregulate IL-6 in the cell and its secretion via enhancing NF-κB in an IGF2-dependent manner in THP-1 macrophages.

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Acknowledgments

This study was supported by the National Natural Sciences Foundation of China (grant numbers 81271905, 81301489, and 81472009).

Conflict of Interest

The authors declare that they have no competing interests.

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    Authors and Affiliations

    1. Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China

      Yan-Chao Wang, Yan-Wei Hu, Yan-Hua Sha, Ji-Juan Gao, Shu-Fen Li, Jia-Yi Zhao, Yu-Rong Qiu, Chuan Huang, Jing-Jing Zhao, Lei Zheng & Qian Wang

    2. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China

      Xin Ma

    3. Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China

      Jing-Bo Lu

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    1. Yan-Chao Wang
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    Correspondence to Lei Zheng or Qian Wang.

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    Yan-Chao Wang and Yan-Wei Hu contributed equally to this work.

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    Wang, YC., Hu, YW., Sha, YH. et al. Ox-LDL Upregulates IL-6 Expression by Enhancing NF-κB in an IGF2-Dependent Manner in THP-1 Macrophages. Inflammation 38, 2116–2123 (2015). https://doi.org/10.1007/s10753-015-0194-1

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    • DOI: https://doi.org/10.1007/s10753-015-0194-1

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