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Insulin Antagonizes LPS-Induced Inflammatory Responses by Activating SR-A1/ERK Axis in Macrophages

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Abstract

Insulin is a key regulator of metabolism and inflammation in the body. However, the mechanism of the anti-inflammatory effect of insulin is not fully understood. In the present study, we investigated the role of the class A1 scavenger receptor (SR-A1), a prototypic member of the pattern recognition receptor family, in the insulin-mediated suppression of inflammatory responses in macrophages. Our murine in vivo studies show that insulin can attenuate lipopolysaccharide (LPS)-induced endotoxemia in a SR-A1-dependent manner, and this was consistent with our in vitro results which demonstrate that the SR-A1 is necessary for insulin to antagonize the LPS-induced inflammatory responses in macrophages. The effect of SR-A1 on the anti-inflammatory action of insulin might be associated with the activation of the extracellular signal-regulated kinases (ERK) signaling pathway in macrophages. Insulin could inhibit macrophage polarization to a pro-inflammatory phenotype via the SR-A1/ERK cascade. Collectively, our results suggest that SR-A1 may be a pivotal element for the anti-inflammation effect of insulin in macrophages.

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Funding

This study was funded by grants from the National Natural Science Foundation of China (81830011, 81670418, and 91739304 to Qi Chen, 81870371 to Jingjing Ben, 81770417 to Xudong Zhu, 81670263 to Xiaoyu Li) and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (18KJA310003 to Jingjing Ben, 15KJA310001 to Xiaoyu Li).

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Author notes

  1. Liu Zhu and Lei Fan contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, No. 101, Longmian Road, Nanjing, 211166, Jiangsu, People’s Republic of China

    Liu Zhu, Lei Fan, Yaqin Zhu, Yan Wang, Hui Bai, Qing Yang, Jingjing Ben, Hanwen Zhang, Xiaoyu Li, Xudong Zhu & Qi Chen

  2. Cardiovascular Medicine Department, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China

    Liu Zhu

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  1. Liu Zhu
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  2. Lei Fan
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  4. Yan Wang
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Correspondence to Xudong Zhu or Qi Chen.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Nanjing Medical University (Permit Number: NJMU/IACUC-1601121).

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Zhu, L., Fan, L., Zhu, Y. et al. Insulin Antagonizes LPS-Induced Inflammatory Responses by Activating SR-A1/ERK Axis in Macrophages. Inflammation 42, 754–762 (2019). https://doi.org/10.1007/s10753-018-0933-1

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