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Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation

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Abstract

Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model. The results showed that plasma SP and IL-17A levels in eczema patients were higher than that in healthy control subject. The percentages of SP+ and NK1R+ expression populations of monocytes, helper T cells, natural killer T cells and basophils in peripheral blood of eczema patients were markedly elevated. It was observed that not only absolute number of mast cells but also SP+ and NK1R+ mast cells are enhanced in the lesion skin of eczema. SP showed a potent chemoattractant action on mast cells as assessed by a mouse peritoneal model and a trans-endothelium cell migration assay. SP-induced mast cell accumulation appears a CD18/CD11a complex, l-selectin and ICAM-1-dependent event which can be blocked by a NK-1R antagonist RP67580. In conclusion, elevated expression of SP in patients with eczema and the ability of SP in induction of mast cell accumulation indicate strongly that SP is a potent proinflammatory mediator, which contributes to the pathogenesis of eczema. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of eczema.

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Abbreviations

ICAM-1:

Intercellular Adhesion Molecule 1

IL:

Interleukin

MFI:

Mean fluorescence intensity

NK1R:

Neurokinin-1 receptor

SP:

Substance P

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Acknowledgements

This project was sponsored by the grants from the “12th Five-Year ” National Science and Technology Support Plan (2014BAI07B02), the National Natural Science Foundation of China (No. 81172836, 81471592, 81472016), Project of Scientific Research Special Fund for Public Industry in Forestry (201304103), Major Science and Technology Platform for Institution of Higher Education in Liaoning province (2014168), “Twelfth five-year” public welfare industry special scientific research project (2015SQ00136), Program for Liaoning Innovation Research Team in University (LNIRT, LT2013017), Climbing Scholar Project for Institution of Higher Education in Liaoning province (2013222), Allergic Disease Translational Medicine Research Center of Liaoning Province (2015225016), Liaoning Provincial Engineering Research Center for Diagnosing & Treating Inflammatory Disease (20141093), Clinical Capability Construction Project for Liaoning Provincial Hospitals (LNCCC-A06-2014, LNCCC-D26-2015), the National Natural Science Foundation of Liaoning Province (2014022027, 2014022019, 201601358) and Science and Technology Planning Project of Suzhou (SYS201272).

Authors’ contribution

Mengmeng Zhan and Wenjiao Zheng carried out most experiments, generated the majority of the data and wrote large part of the first draft of the paper. Qijun Jiang and Zuotao Zhao took part in the clinical study and participated in data analysis and study design. Junling Wang and Zhiyun Wang took part in ELISA, flow cytometry, immunochemistry, cell culture and challenge test and wrote a part of the first draft of the paper. Huiyun Zhang and Shaoheng He designed and conducted the study, analyzed the data and wrote the second and final drafts of the paper. All authors read and approved the final paper.

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Authors and Affiliations

  1. Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People’s Republic of China

    Mengmeng Zhan, Wenjiao Zheng, Zhiyun Wang, Junling Wang, Huiyun Zhang & Shaoheng He

  2. Department of Dermatology, Donggang Central Hospital, Donggang, Liaoning, 118300, China

    Qijun Jiang

  3. Department of Dermatology and Venerology, Peking University First Hospital, Beijing, 100000, China

    Zuotao Zhao

  4. Department of pathophysiology, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China

    Huiyun Zhang

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  1. Mengmeng Zhan
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  2. Wenjiao Zheng
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Correspondence to Shaoheng He.

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The informed consent from each volunteer according to the Declaration of Helsinki and agreement with the ethical committee of the First Affiliated Hospital of Jinzhou Medical University were obtained.

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The authors declare that they have no conflict of interest.

Additional information

Mengmeng Zhan and Wenjiao Zheng contributed equally to this work.

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Zhan, M., Zheng, W., Jiang, Q. et al. Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation. Cell Biol Toxicol 33, 389–405 (2017). https://doi.org/10.1007/s10565-016-9379-0

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