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Anti-inflammatory activity of extensively hydrolyzed casein is mediated by granzyme B

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Abstract

Objective

Nutritional factors such as extensively hydrolyzed casein (eHC) have been proposed to exert anti-inflammatory activity and affect clinical outcomes such as tolerance development in cow’s milk allergy. Granzyme B (GrB) induces apoptosis in target cells and also controls the inflammatory response. Whether eHC could affect the activity of granzyme B and play a role in GrB-mediated inflammatory responses in vitro was unknown.

Methods

The activity of GrB was measured using the substrate Ac-IEPD-pNA. Inflammatory responses were induced with GrB in HCT-8 and THP-1 cells, and pro-inflammatory cytokines were determined at the transcriptional and protein level.

Results

GrB could induce the expression of IL-1β in HCT-8 cells, and IL-8 and MCP-1 in THP-1 cells, respectively. Interestingly, GrB acted synergistically on LPS-induced inflammation in HCT-8 cells and eHC reduced pro-inflammatory responses in both GrB and LPS-mediated inflammation. Further analyses revealed that eHC could inhibit the biological activities and cytotoxic activities of GrB and then could reduce GrB-mediated inflammatory response.

Conclusion

The results from the current study suggest that anti-inflammatory activity of extensively hydrolyzed casein is, to a certain extent, mediated through modulation of granzyme B activity and responses.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (81771306, 81072459), National Key Research and Development Program of China (2016YFC1200400), Mead Johnson Nutrition (MJN).

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Authors and Affiliations

  1. Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China

    Xuefei Hu & Wenzheng Jiang

  2. Global Discovery Department, Mead Johnson Pediatric Nutrition Institute, Middenkampweg 2, 6545 CJ, Nijmegen, The Netherlands

    Yan Zhong & Tim T. Lambers

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  1. Xuefei Hu
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  2. Yan Zhong
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Hu, X., Zhong, Y., Lambers, T.T. et al. Anti-inflammatory activity of extensively hydrolyzed casein is mediated by granzyme B. Inflamm. Res. 68, 715–722 (2019). https://doi.org/10.1007/s00011-019-01254-8

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  • DOI: https://doi.org/10.1007/s00011-019-01254-8

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