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Luteolin Alters Macrophage Polarization to Inhibit Inflammation

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Abstract

Luteolin is a natural flavonoid compound derived from vegetables, fruits, and herbs with potent anti-inflammatory activity. Macrophage polarization is important in the development and progression of inflammation. However, whether luteolin can inhibit inflammation by regulating the polarized phenotypes of macrophages remains unknown. The aim of this study was to investigate the effects of luteolin on the inflammatory polarization of macrophages and the underlying mechanisms. RAW264.7 macrophages were induced to M1 polarization by stimulation with lipopolysaccharide plus interferon-γ or to M2 polarization with interleukin 4 (IL-4), simultaneously, accompanied with different concentrations of luteolin. Laser confocal microscopy was used to observe cell morphology; flow cytometry was employed to detect the expression of membrane surface molecule CD86 and CD206; qPCR was performed to examine the mRNA expression of M1 markers (iNOS, IL-1β, IL-6) and M2 markers (Arg1, CD206, CD163, IL-10, and IL-13), respectively; ELISA was used to examine the levels of IL-6, TNF-α, and IL-10; and Western blotting was used to evaluate the p-STAT3 and p-STAT6 protein pathway. The morphology of activated M1 macrophages changed significantly, developing dendritic characteristics. After luteolin treatment, the expression of M1-type proinflammatory mediators and the surface marker CD86 were decreased evidently, but those of M2-related anti-inflammatory factors and CD206 were increased markedly. Moreover, p-STAT3 was downregulated and p-STAT6 was upregulated in a dose-dependent manner. Conclusion, luteolin can alter the M1/M2 polarization of macrophages, thereby playing an anti-inflammatory role via downregulation of p-STAT3 and upregulation of p-STAT6. Therefore, luteolin may be potentially valuable to inhibit inflammation.

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Abbreviations

LPS :

Lipopolysaccharide

IFN-γ :

Interferon-γ

iNOS :

Inducible nitric oxide synthase

IL-1β :

Interleukin-1β

CD :

Cluster of differentiation

TNF :

Tumor necrosis factor

STAT :

Signal transducer and activator of transcription

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Funding

This work was supported by National Natural Science Foundation of China (grant number 81673945; 81471010) and the Project of Jiangsu Branch of China Academy of Chinese Medical Sciences (FY201809).

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Author notes

  1. Shuxia Wang and Meng Cao contributed equally to this work.

Authors and Affiliations

  1. Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China

    Shuxia Wang, Jianfeng Shi & Xiaoming Yao

  2. Laboratory of Cellular and Molecular Biology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China

    Meng Cao

  3. Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China

    Shuhang Xu, Xiaodong Mao & Chao Liu

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  1. Shuxia Wang
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Correspondence to Xiaoming Yao or Chao Liu.

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Wang, S., Cao, M., Xu, S. et al. Luteolin Alters Macrophage Polarization to Inhibit Inflammation. Inflammation 43, 95–108 (2020). https://doi.org/10.1007/s10753-019-01099-7

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