AUTHOR=Gu Kefei , Wang Tan , Peng Liying , Zhao Yueliang 

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

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.881924

DOI=10.3389/fnut.2022.881924

ISSN=2296-861X

ABSTRACT=<p><italic>FIP-fve</italic>, a fungal fruiting body protein from <italic>Flammulina velutipes</italic>, has potential immunomodulatory properties. Here, we investigated the immunomodulation mechanism of <italic>FIP-fve</italic> 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 <italic>FIP-fve</italic> 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 <italic>FIP-fve</italic> 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 <italic>FIP-fve</italic> enhanced cell proliferation and IL-2 release in Jurkat E6-1 cells. Our results demonstrate that <italic>FIP-fve</italic> stimulates cell proliferation and enhances IL-2 secretion through MAP2K3/p38α activation.</p>