title: Interleukin-18 and its receptor are expressed in gonadotropin-releasing hormone neurons of mouse and rat forebrain.
abstract: Interleukin-18 (IL-18) is a pro-inflammatory cytokine and an important mediator of peripheral inflammation and host immune response. IL-18 functions through its binding with the IL-18 receptor (IL-18R), which consists of two chains, an IL-18-binding α chain (IL-18Rα) and a signaling β chain. IL-18 and IL-18R are expressed in the brain; however, limited information is available on IL-18R expression and the role of IL-18 in neurosecretory cells. In the present study, we used immunohistochemical techniques to investigate the distribution of IL-18Rα and IL-18 in the hypothalamus of male mice and rats. IL-18Rα-positive and IL-18-positive perikarya and fibers were found scattered throughout the medial septal nucleus, the nuclei of the vertical and horizontal limbs of the diagonal band, the organum vasculosum of the laminae terminalis, the preoptic area, and the anterior hypothalamic area. It is well known that gonadotropin-releasing hormone (GnRH) neuronal somata and/or fibers are found in these regions. Therefore, we performed double-label immunofluorescence for IL-18Rα/IL-18 and GnRH. IL-18Rα was expressed in approximately 60% of GnRH-immunopositive perikarya, and IL-18 was distributed in all GnRH-immunopositive perikarya. These observations suggest that IL-18 exerts direct effects upon the GnRH neuron via IL-18Rα and acts on GnRH neurons through an autocrine or paracrine pathway.
authors.affiliation: Department of Anatomy and Cell Biology, Hyogo College of Medicine, Hyogo 663-8501, Japan. Electronic address: sachik@hyo-med.ac.jp.
authors.forename: Sachi
authors.initials: S
authors.lastname: Kuwahara-Otani
authors.affiliation: Department of Anatomy and Cell Biology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Anatomy and Cell Biology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Minato
authors.affiliation: Department of Anatomy and Cell Biology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Neuropsychiatry, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Yamanishi
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hata
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Department of Anatomy and Cell Biology, Hyogo College of Medicine, Hyogo 663-8501, Japan. Electronic address: h-yagi@hyo-med.ac.jp.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Yagi
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053724:Receptors, Interleukin-18 / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D020382:Interleukin-18; D053724:Receptors, Interleukin-18; D007987:Gonadotropin-Releasing Hormone
keywords: GnRH neuron; Hypothalamus; IL-18; IL-18Rα