The inhibitory function of Fc-ST2 depends on cell type; IL-1RAcP and ST2 are necessary but insufficient for IL-33 activity

Immunol Res. 2013 May;56(1):122-30. doi: 10.1007/s12026-013-8388-9.

Abstract

IL-33 (IL-1F11) is a member of IL-1 family ligand, which stimulates the production of inflammatory cytokines. IL-33 receptor complex is comprised of IL-1 receptor accessory protein (IL-1RAcP) and ST2 that are activated by IL-33 ligand binding. ST2 is a ligand-binding chain of the IL-33 receptor component, and the soluble ST2 form possesses antagonistic activity. Here, we expressed the extracellular domain of ST2-fused to the immunoglobulin of IgG1 constant region in order to generate a soluble recombinant Fc-ST2. Human and mouse recombinant Fc-ST2 protein were expressed in Chinese hamster ovary cells and purified using a mini-protein A affinity chromatography. The recombinant Fc-ST2 protein was used to examine inhibitory function in IL-33-induced cytokine production in different cell types. The human Fc-ST2 abolished IL-33-induced IL-8 production in human mast cells, but mouse Fc-ST2 failed to inhibit IL-33-induced TNFα production in mouse Raw 264.7 macrophage cells. We further investigated the expression of IL-33 receptor component with various cell lines. IL-33 receptors expression pattern and Fc-ST2 inhibitory activity in different cell types suggest that IL-1RAcP and ST2 are necessary but insufficient for IL-33 activity. Our results suggest that an additional receptor component may participate in the biological activity of IL-33.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Chromatography, Affinity
  • Cricetinae
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / metabolism*
  • Interleukin-1 Receptor Accessory Protein / immunology*
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-8 / metabolism
  • Interleukins / immunology*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mice
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology*
  • Recombinant Fusion Proteins / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Species Specificity
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • IL1RL1 protein, human
  • IL33 protein, human
  • Il1rl1 protein, mouse
  • Immunoglobulin Fc Fragments
  • Interleukin-1 Receptor Accessory Protein
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-8
  • Interleukins
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha