Enhancement of natural killer activity and IFN-γ production in an IL-12-dependent manner by a Brassica rapa L

Biosci Biotechnol Biochem. 2018 Apr;82(4):654-668. doi: 10.1080/09168451.2017.1408396. Epub 2017 Dec 6.

Abstract

Certain food components possess immunomodulatory effects. The aim of this study was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa L. We demonstrated an enhancement of natural killer (NK) activity and interferon (IFN)-γ production in mice that were orally administered an insoluble fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced IFN-γ production in mouse spleen cells in an interleukin (IL)-12-dependent manner, and NK1.1+ cells were the main cells responsible for producing IFN-γ. Additionally, the results suggested that the active compounds in the insoluble fraction were recognized by Toll-like receptor (TLR) 2, TLR4, and C-type lectin receptors on dendritic cells, and they activated signaling cascades such as MAPK, NF-κB, and Syk. These findings suggest that B. rapa L. is a potentially promising immuno-improving material, and it might be useful for preventing immunological disorders such as infections and cancers by activating innate immunity.

Keywords: APCs, antigen-presenting cells; BMDCs, bone marrow-derived dendritic cells; BW, body weight; Brassica rapa L.; CFSE, carboxyfluorescein diacetate succinimidyl ester; CLRs, C-type lectin receptors; Con A, concanavalin A; Cyto D, cytochalasin D; DCs, dendritic cells; EDTA, ethylenediamine-N,N,N′,N′,-tetraacetic acid; ELISA, enzyme-linked immunosorbent assay; ERK, extracellular signal-related kinase; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; JNK, jun kinase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MHC, major histocompatibility complex; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NK, natural killer; PB, polymyxin B; PBS, phosphate-buffered saline; PE, phycoerythrin; PGN, peptidoglycan; PI, propidium iodide; PPs, Peyer’s patches; RPMI, Roswell Park Memorial Institute; SD, standard deviation; Syk, spleen tyrosine kinase; TCR, T cell receptor; TLRs, Toll-like receptors; TNF, tumor necrosis factor; WT, wild-type; dendritic cells; i.p., intraperitoneally; immunomodulation; interferon-γ; mAbs, monoclonal antibodies; mLNs, mesenteric lymph nodes; natural killer cell activity.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Administration, Oral
  • Animals
  • Brassica rapa / metabolism*
  • Cytokines / metabolism
  • Female
  • Functional Food*
  • Interferon-gamma / biosynthesis*
  • Interleukin-12 / physiology*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Lectins, C-Type / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Signal Transduction
  • Spleen / drug effects
  • Spleen / metabolism
  • Syk Kinase / metabolism
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Lectins, C-Type
  • NF-kappa B
  • Plant Extracts
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Interleukin-12
  • Interferon-gamma
  • Syk Kinase
  • Mitogen-Activated Protein Kinases