Enhanced production of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis

J Oral Biosci. 2022 Sep;64(3):366-375. doi: 10.1016/j.job.2022.05.007. Epub 2022 Jun 3.

Abstract

Objectives: In this report, we attempt to clarify the immune modulatory effects of Brazilian green propolis (BGP) and its major component, artepillin C, on the cytokine production of anti-CD3 antibody-stimulated mouse spleen cells. We also estimate the physiological mechanism affecting artepillin C's upon the cells.

Methods: Male C3H/HeN mouse spleen cells stimulated by antiCD3 monoclonal antibody were co-cultured with BGP, artepillin C, and HC030031, a transient receptor potential ankyrin 1 (TRPA1) Ca2+ channel antagonist. The synthesis of interferon (IFN)-γ, interleukin (IL)-6, IL-17, IL-4, IL-10, and IL-2 was assayed by enzyme-linked immunoassay. The expression of IL-2 mRNA and the protein product were examined by reverse transcription-quantitative polymerase chain reaction and Western blot analyses, respectively.

Results: The production of IL-2 was markedly enhanced, while that of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6, and IL-17 was significantly reduced in the antibody-stimulated spleen cells treated with BGP at a non-cytostatic concentration. These effects were reproduced in the cells treated with artepillin C. The expression of IL-2 mRNA was unaffected; however, that of the protein was significantly enhanced in the artepillin C-treated cells compared to untreated control cells. The enhancement of protein expression and the production of IL-2 by artepillin C was significantly alleviated by adding HC030031.

Conclusions: Artepillin C is an important regulator of cytokine synthesis from activated spleen cells. The agent specifically augmented the expression of IL-2 via the Ca2+-permeable cation channel, TRPA1, at least in part, at the translational or secretion levels.

Keywords: Artepillin C; Brazilian green propolis (BGP); IL-2; Spleen cells; TRPA1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides
  • Animals
  • Ankyrins
  • Antibodies, Monoclonal
  • Brazil
  • Interferons
  • Interleukin-17
  • Interleukin-2
  • Interleukin-4
  • Interleukin-6
  • Male
  • Mice
  • Mice, Inbred C3H
  • Phenylpropionates
  • Propolis* / pharmacology
  • Purines
  • RNA, Messenger
  • Spleen
  • TRPA1 Cation Channel

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Ankyrins
  • Antibodies, Monoclonal
  • Interleukin-17
  • Interleukin-2
  • Interleukin-6
  • Phenylpropionates
  • Purines
  • RNA, Messenger
  • TRPA1 Cation Channel
  • Interleukin-4
  • artepillin C
  • Interferons
  • Propolis