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Adenosine effectively restores endotoxin-induced inhibition of human neutrophil chemotaxis via A1 receptor-p38 pathway

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Abstract

Neutrophil chemotaxis plays an essential role in recruiting neutrophils to sites of inflammation. Neutrophil chemotaxis is suppressed both after exposure to lipopolysaccharide (LPS) in vitro and during clinical and experimental endotoxemia, leading to serious consequences. Adenosine (ADO) is a potent anti-inflammatory agent that acts on a variety of neutrophil functions. However, its effects on human neutrophil chemotaxis during infection have been less well characterized. In the present study, we investigated the effect of ADO and its receptor-specific antagonist and agonist on neutrophil chemotaxis in an in vitro LPS-stimulated model. The results showed that increasing the concentration of ADO effectively restored the LPS-inhibited neutrophil chemotaxis to IL-8. A similar phenomenon occurred after intervention with a selective A1 receptor agonist but not with a selective antagonist. Pre-treatment with cAMP antagonist failed to restore LPS-inhibited chemotaxis. Furthermore, protein array and western blot analysis showed that the activation of A1 receptor significantly decreased LPS-induced p38 MAPK phosphorylation. However, the surface expression of the A1 receptor in LPS-stimulated neutrophils was not significantly changed. Taken together, these data indicated that ADO restored the LPS-inhibited chemotaxis via the A1 receptor, which downregulated the phosphorylation level of p38 MAPK, making this a promising new therapeutic strategy for infectious diseases.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China, No. 81071546, No. 81272148, No. 81171786, No. 81471903 and No. 81301657.

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Authors and Affiliations

  1. Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, China

    Xiaohan Xu, Xu Wang, Weiting Qin, Huafeng Zhang & Bingwei Sun

  2. Department of Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

    Shuyun Zheng

  3. Department of Clinical Laboratory, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, China

    Yuyun Xiong

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  1. Xiaohan Xu
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  2. Shuyun Zheng
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  3. Yuyun Xiong
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Correspondence to Bingwei Sun.

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Responsible Editor: Bernhard Gibbs.

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Xu, X., Zheng, S., Xiong, Y. et al. Adenosine effectively restores endotoxin-induced inhibition of human neutrophil chemotaxis via A1 receptor-p38 pathway. Inflamm. Res. 66, 353–364 (2017). https://doi.org/10.1007/s00011-016-1021-3

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  • DOI: https://doi.org/10.1007/s00011-016-1021-3

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