IL-33 can promote survival, adhesion and cytokine production in human mast cells

Lab Invest. 2007 Oct;87(10):971-8. doi: 10.1038/labinvest.3700663. Epub 2007 Aug 13.


IL-33 is a recently identified member of the IL-1 family of molecules, which also includes IL-1 and IL-18. IL-33 binds to the receptor, T1/ST2/IL-1R4, and can promote cytokine secretion by Th2 cells and NF-kappaB phosphorylation in mouse mast cells. However, the effects of these molecules, especially IL-33, in human mast cells are poorly understood. Expression of the receptors for IL-1 family molecules, specifically, IL-1R1, IL-18R and T1/ST2, was detectable intracellularly in human umbilical cord blood-derived mast cells (HUCBMCs) by flow cytometry, but was scarcely detectable on the cells' surface. However, IL-1beta, IL-18 or IL-33 induced phosphorylation of Erk, p38 and JNK in naïve HUCBMCs, and IL-33 or IL-1beta, but not IL-18, enhanced the survival of naive HUCBMCs and promoted their adhesion to fibronectin. IL-33 or IL-1beta also induced IL-8 and IL-13 production in naïve HUCBMCs, and enhanced production of these cytokines in IgE/anti-IgE-stimulated HUCBMCs, without enhancing secretion of either PGD(2) or histamine. Moreover, IL-33-mediated IL-8 production by HUCBMCs was markedly reduced by the p38 MAPK inhibitor, SB203580. In contrast to findings with mouse mast cells, IL-18 neither induced nor enhanced secretion of the mediators PGD(2) or histamine by HUCBMCs. Our findings identify previously unknown functions of IL-33 in human mast cells. One of these is that IL-33, like IL-1beta, can induce cytokine production in human mast cells even in the absence of stimuli of FcepsilonRI aggregation. Our findings thus support the hypothesis that IL-33 may enhance mast cell function in allergic disorders and other settings, either in the presence or absence of co-stimulation of mast cells via IgE/antigen-FcepsilonRI signals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / physiology
  • Cell Survival / physiology
  • Cells, Cultured
  • Fibronectins / physiology*
  • Histamine Release / physiology
  • Humans
  • Interleukin-13 / metabolism*
  • Interleukin-18 / physiology
  • Interleukin-1beta / physiology
  • Interleukin-33
  • Interleukin-8 / metabolism*
  • Interleukins / metabolism
  • Interleukins / physiology*
  • Mast Cells / metabolism
  • Mast Cells / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Prostaglandin D2 / metabolism
  • Receptors, Interleukin-1 / metabolism


  • Fibronectins
  • IL33 protein, human
  • Interleukin-13
  • Interleukin-18
  • Interleukin-1beta
  • Interleukin-33
  • Interleukin-8
  • Interleukins
  • Receptors, Interleukin-1
  • Mitogen-Activated Protein Kinases
  • Prostaglandin D2