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Luteolin suppresses inflammation through inhibiting cAMP-phosphodiesterases activity and expression of adhesion molecules in microvascular endothelial cells

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Abstract

Luteolin, an anti-inflammatory ingredient found in the Chinese herb Folium perillae, can inhibit not only the cyclic adenosine monophosphate (cAMP)-phosphodiesterases (PDEs) activity of neutrophils, but also the expression of lymphocyte function-associated antigen-1 in neutrophils, both of which result in a decrease in the adhesion between neutrophils and microvascular endothelial cells. However, the effect of luteolin on the cAMP-PDEs activity and expression of adhesion molecules in endothelial cells are not clear. In the present study, primary rat pulmonary microvascular endothelial cells and a lipopolysaccharide-induced rat acute pneumonia model were used to explore the role of luteolin on cAMP-PDEs activity, expression of adhesion molecules, and leukocyte infiltration. We demonstrate that rat pulmonary microvascular endothelial cells expressed high levels of cAMP-PDEs, specifically PDE4, and further luteolin exhibited dose-dependent inhibition on the activity of cAMP-PDEs or PDE4 in endothelial cells. Luteolin also had a significant inhibitory effect on the expression of vascular cell adhesion molecule (VCAM)-1, but not intracellular cell adhesion molecule (ICAM)-1 in microvascular endothelial cells. Further, we show that luteolin decreased the levels of soluble ICAM-1 (sICAM-1), but not soluble E-selectin in the serum of rats subjected to acute pneumonia. We also show that luteolin treatment decreased the wet/dry weight ratio of lung tissue and reduced the total number of serum leukocytes in a dose-dependent manner in a rat acute pneumonia model. In conclusion, these results demonstrate that luteolin suppresses inflammation, at least in part, through inhibiting both cAMP-PDEs or PDE4 activity and the expression of VCAM-1 (in vitro) and sICAM-1 (in vivo) in endothelial cells.

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Acknowledgements

The research was financially supported by the National Natural Science Foundation of China (No. 31540059/31101851).

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  1. Xueli Kong and Guitao Huo contributed equally to this work.

Authors and Affiliations

  1. Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, 7 Beinong Road, Huilongguan Town, Changping District, Beijing, 102206, China

    Xueli Kong, Shurong Liu, Fengnan Li, Wu Chen & Daixun Jiang

  2. National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, 100050, China

    Guitao Huo

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  1. Xueli Kong
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  2. Guitao Huo
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  3. Shurong Liu
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  4. Fengnan Li
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  5. Wu Chen
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Correspondence to Daixun Jiang.

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Kong, X., Huo, G., Liu, S. et al. Luteolin suppresses inflammation through inhibiting cAMP-phosphodiesterases activity and expression of adhesion molecules in microvascular endothelial cells. Inflammopharmacol 27, 773–780 (2019). https://doi.org/10.1007/s10787-018-0537-2

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  • DOI: https://doi.org/10.1007/s10787-018-0537-2

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