title: Proinsulin Shares a Motif with Interleukin-1α (IL-1α) and Induces Inflammatory Cytokine via Interleukin-1 Receptor 1.
abstract: Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1.
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and.
authors.forename: Siyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and.
authors.forename: Eunsom
authors.initials: E
authors.lastname: Kim
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea.
authors.forename: Hyunjhung
authors.initials: H
authors.lastname: Jhun
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Hong
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Kwak
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Jo
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and.
authors.forename: Suyoung
authors.initials: S
authors.lastname: Bae
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and.
authors.forename: Jongho
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and.
authors.forename: Busun
authors.initials: B
authors.lastname: Kim
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and.
authors.forename: Jungmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and.
authors.forename: Sulah
authors.initials: S
authors.lastname: Youn
authors.affiliation: Division of Nephrology, Department of internal medicine, Jeju National University, 63243 Jeju-si, Jeju-do, Korea.
authors.forename: Somi
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of internal medicine, Jeju National University, 63243 Jeju-si, Jeju-do, Korea.
authors.forename: Miyeon
authors.initials: M
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of internal medicine, Jeju National University, 63243 Jeju-si, Jeju-do, Korea.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Medicine, Pusan Paik Hospital, Collage of Medicine, Inje University, Busan 47392, Korea, and.
authors.forename: Youngmin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea.
authors.forename: Dong-Ki
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea.
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Kim
authors.affiliation: From the Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology and College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea, soohyun@konkuk.ac.kr.
authors.forename: Soohyun
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D018836:Inflammation Mediators / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D011384:Proinsulin / Q000737:chemistry / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D017472:Receptors, Interleukin-1; D011384:Proinsulin
keywords: cytokine; insulin; interleukin 1 (IL-1); protein motif; toll/interleukin-1 receptor (TIR)*