title: The inhibitory function of Fc-ST2 depends on cell type; IL-1RAcP and ST2 are necessary but insufficient for IL-33 activity.
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.
authors: Department of Biomedical Science and Technology, Konkuk University, Gwangjin-gu, Seoul, Korea.
authors: Kwangwon
authors: K
authors: Hong
authors: Youngmin
authors: Y
authors: Lee
authors: Siyoung
authors: S
authors: Lee
authors: Sungnoh
authors: S
authors: Hong
authors: Suyoung
authors: S
authors: Bae
authors: Jaewoo
authors: J
authors: Hong
authors: Jida
authors: J
authors: Choi
authors: Hyunjhung
authors: H
authors: Jhun
authors: Areum
authors: A
authors: Kwak
authors: Eunsom
authors: E
authors: Kim
authors: Seunghyun
authors: S
authors: Jo
authors: Taebong
authors: T
authors: Kang
authors: You Sook
authors: YS
authors: Cho
authors: Yong-Gil
authors: YG
authors: Kim
authors: Soohyun
authors: S
authors: Kim
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity; D006224:Cricetinae; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism*; D053577:Interleukin-1 Receptor Accessory Protein / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; C486189:Il1rl1 protein, mouse; D007141:Immunoglobulin Fc Fragments; D053577:Interleukin-1 Receptor Accessory Protein; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016209:Interleukin-8; D007378:Interleukins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha