title: Reconstitution of ST2 (IL-1R4) specific for IL-33 activity; no suppression by IL-1Ra though a common chain IL-1R3 (IL-1RAcP) shared with IL-1.
abstract: Interleukin-33 (IL-33) receptors are composed of ST2 (also known as IL-1R4), a ligand binding chain, and IL-1 receptor accessory protein (IL-1RAcP, also known as IL-1R3), a signal transducing chain. IL-1R3 is a common receptor for IL-1α, and IL-1β, IL-33, and three IL-36 isoforms. A549 human lung epithelial cells are highly sensitive to IL-1α and IL-1β but not respond to IL-33. The lack of responsiveness to IL-33 is due to ST2 expression. ST2 was stably transfected into A549 cells to reconstitute its activity. RT-PCR and FACS analysis confirmed ST2 expression on the cell surface of A549/ST2 cells. Upon IL-33 stimulation, A549/ST2 cells induced IL-8 and IL-6 production in a dose dependent manner while A549/mock cells remained unresponsive. There was no difference in IL-1α and IL-1β activity in A549/ST2 cells compared to A549/mock cells despite the fact that IL-33 shares IL-1R3 with IL-1α/β. IL-33 activated inflammatory signaling molecules in a time- and dose-dependent manner. Anti-ST2 antibody and soluble recombinant ST2-Fc abolished IL-33-induced IL-6 and IL-8 production in A549/ST2 cells but the IL-1 receptor antagonist failed to block IL-33-induced cytokines. This result demonstrates for the first time the reconstitution of ST2 in A549 human lung epithelial cell line and verified its function in IL-33-mediated cytokine production and signal transduction.
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Jo
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Eunsom
authors.initials: E
authors.lastname: Kim
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Kwak
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jungmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Hong
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jongho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Sulah
authors.initials: S
authors.lastname: Youn
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Suyoung
authors.initials: S
authors.lastname: Bae
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Busun
authors.initials: B
authors.lastname: Kim
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Soyoon
authors.initials: S
authors.lastname: Ryoo
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chung-Ju 380-701, Republic of Korea.
authors.forename: Tae-Bong
authors.initials: TB
authors.lastname: Kang
authors.affiliation: Department of Immunology, Konkuk University, Chung-Ju 380-701, Republic of Korea.
authors.forename: Erk
authors.initials: E
authors.lastname: Her
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Dong-Ki
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Medicine, Pusan Paik Hospital, Collage of Medicine, Inje University, Busan 633-165, Republic of Korea.
authors.forename: Youngmin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Hyunjhung
authors.initials: H
authors.lastname: Jhun
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: soohyun@konkuk.ac.kr.
authors.forename: Soohyun
authors.initials: S
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D005786:Gene Expression Regulation / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C508606:CXCL8 protein, human; C508584:IL1A protein, human; C508585:IL1B protein, human; C079241:IL1RL1 protein, human; C507763:IL1RN protein, human; C506536:IL33 protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D000067596:Interleukin-33; D015850:Interleukin-6; D016209:Interleukin-8
keywords: A549/ST2 cells; IL-1; IL-1R3; IL-1Ra; IL-33