title: Proton receptor GPR68 expression in dendritic-cell-like S100β-positive cells of rat anterior pituitary gland: GPR68 induces interleukin-6 gene expression in extracellular acidification.
abstract: S100β-positive cells, which do not express the classical pituitary hormones, appear to possess multifunctional properties and are assumed to be heterogeneous in the anterior pituitary gland. The presence of several protein markers has shown that S100β-positive cells are composed of populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. Recently, we succeeded in separating S100β-positive cells into round-cell (dendritic-cell-like) and process-cell types. We also found the characteristic expression of anti-inflammatory factors (interleukin-6, Il-6) and membrane receptors (integrin β-6) in the round type. Here, we further investigate the function of the subpopulation of S100β-positive cells. Since IL-6 is also a paracrine factor that regulates hormone producing-cells, we examine whether a correlation exists among extracellular acid stress, IL-6 and hormone production by using primary cultures of anterior pituitary cells. Dendritic-cell-like S100β-positive cells notably expressed Gpr68 (proton receptor) and Il-6. Furthermore, the expression of Il-6 and proopiomelanocortin (Pomc) was up-regulated by extracellular acidification. The functional role of IL-6 and GPR68 in the gene expression of Pomc during extracellular acidification was also examined. Small interfering RNA for Il-6 up-regulated Pomc expression and that for Gpr68 reversed the down-regulation of Il-6 and up-regulated Pomc expression by extracellular acidification. Thus, S100β-positive dendritic-like cells can sense an increase in extracellular protons via GPR68 and respond by the production of IL-6 in order to suppress the up-regulation of Pomc expression.
authors.affiliation: Laboratory of Anatomy and Cell Biology, Department of Health Sciences, Kyorin University, 476 Miyashita-cho, Hachioji, Tokyo, 192-8508, Japan, kota@ks.kyorin-u.ac.jp.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Higuchi
authors.forename: Saishu
authors.initials: S
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakakura
authors.forename: Kozue
authors.initials: K
authors.lastname: Tateno
authors.forename: Rumi
authors.initials: R
authors.lastname: Hasegawa
authors.forename: Shu
authors.initials: S
authors.lastname: Takigami
authors.forename: Shunji
authors.initials: S
authors.lastname: Ohsako
authors.forename: Takako
authors.initials: T
authors.lastname: Kato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D000143:Acids / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006863:Hydrogen-Ion Concentration; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000378:metabolism; D011522:Protons; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism*
chemical_list: D000143:Acids; D015850:Interleukin-6; C000590690:LOC102553138 protein, rat; D011522:Protons; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D064568:S100 Calcium Binding Protein beta Subunit