Genistein inhibits pro‑inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway

Int J Mol Med. 2014 Dec;34(6):1669-74. doi: 10.3892/ijmm.2014.1956. Epub 2014 Oct 2.


Anaphylaxis is a rapidly occurring allergic reaction to any foreign substance, including venom from insects, foods and medications, which may cause fatalities. To prevent anaphylaxis, these triggers must be avoided. However, avoidance of numerous triggers is difficult. For this reason, the development of immunotherapeutic adjuvants that suppress the allergic response is important for anaphylaxis control. Mast cells are one of the major inflammatory cells involved in the inflammatory response, which secrete several inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, and recruits other immune cells. Mast cells are also involved in a number of diseases, such as sinusitis, rheumatoid arthritis and asthma. Genistein, a phytoestrogen, has been reported to have anti-oxidative and anti-inflammatory activities. However, the effects of genistein on the anti-inflammatory response of mast cells remain unknown. In the present study, the anti-inflammatory effects of genistein on mast cells were investigated. Genistein significantly decreased IL-6 and IL-1β mRNA levels, as well as IL-6 production in PMA/A23187-induced mast cells activation. In addition, genistein inhibited the phosphorylation of ERK 1/2 in PMA/A23187-induced mast cell activation. However, phosphorylation of p38 was not altered. Thus, these findings indicate that genistein inhibited the inflammatory status of mast cells through inhibition of the ERK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcimycin / pharmacology
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genistein / pharmacology*
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation / drug effects
  • Phytoestrogens / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Cytokines
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Phytoestrogens
  • Tumor Necrosis Factor-alpha
  • Calcimycin
  • Genistein
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate