FIP-fve Stimulates Cell Proliferation and Enhances IL-2 Release by Activating MAP2K3/p38α (MAPK14) Signaling Pathway in Jurkat E6-1 Cells

Kefei Gu; Tan Wang; Liying Peng; Yueliang Zhao

doi:10.3389/fnut.2022.881924

FIP-fve Stimulates Cell Proliferation and Enhances IL-2 Release by Activating MAP2K3/p38α (MAPK14) Signaling Pathway in Jurkat E6-1 Cells

Front Nutr. 2022 May 9:9:881924. doi: 10.3389/fnut.2022.881924. eCollection 2022.

Authors

Kefei Gu¹, Tan Wang^{1

2

3}, Liying Peng⁴, Yueliang Zhao^{2

3}

Affiliations

¹ Institute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai, China.
² College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.
³ Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), Ministry of Agriculture, Shanghai, China.
⁴ Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Science, Shanghai, China.

Abstract

FIP-fve, a fungal fruiting body protein from Flammulina velutipes, has potential immunomodulatory properties. Here, we investigated the immunomodulation mechanism of FIP-fve in Jurkat E6-1 cells by conducting a cell viability assay and IL-2 release assay. Kinase inhibitors experiment and proteomics analysis were also involved in the mechanism study. It was found that FIP-fve stimulated cell proliferation and enhanced IL-2 secretion in a dose-dependent manner in Jurkat E6-1 cells. Unbiased high-throughput proteomics analysis showed that 4 T cell immune activation markers, including ZAP-70, CD69, CD82, and KIF23, were upregulated in response to FIP-fve treatment. Further pathway analysis indicated that MAP2K3/p38 pathway-related proteins, including MAP2K, p38, ELK, AATF, FOS, and JUN-B, were unregulated. In addition, losmapimod (p38 inhibitor) and gossypetin (MAP2K3 inhibitor) inhibited FIP-fve enhanced cell proliferation and IL-2 release in Jurkat E6-1 cells. Our results demonstrate that FIP-fve stimulates cell proliferation and enhances IL-2 secretion through MAP2K3/p38α activation.

Keywords: FIP-fve; IL-2; MAP2K3/p38α; immunomodulation mechanism; proteomics analysis.