title: Pituitary adenylate cyclase-activating peptide (PACAP) stimulates production of interleukin-6 in rat Müller cells.
abstract: Pituitary adenylate cyclase-activating peptide (PACAP) is known to regulate not only neurons but also astrocytes. Here, we investigated, both in vitro and in vivo, the effects of PACAP38 on rat Müller cells, which are the predominant glial element in the retina. Müller cells isolated from juvenile Wistar rats were treated with PACAP38 or PACAP6-38, a PACAP selective antagonist. Cell proliferation was determined by measuring the incorporation of bromodeoxyuridine with ELISA. Interleukin-6 (IL-6) levels in the culture medium were determined by a bioassay using B9 cells, IL-6 dependent hybridoma. In adult Wistar rats, the expression of IL-6 in the retina after intravitreal injection of PACAP38 (10 pmol) was assessed by immunohistochemistry. PACAP38 stimulated IL-6 production in Müller cells at a concentration as low as 10(-12) M, which did not induce cell proliferation. This elevation of IL-6 production was inhibited by PACAP6-38. Radial IL-6 expression was observed throughout the retina at 2 and 3 days after PACAP38 injection. These data demonstrate that Müller cells are one of the target cells for PACAP. IL-6, which is released from Müller cells with stimulation by PACAP, may play a significant role in the retina.
authors.affiliation: Bioengineering Institute, Assessment Research Department, Nidek Co. Ltd., 6-209-1 Miyakitadori Gamagori-shi, Aichi 443-0022, Japan. masayoshi_nakatani@nidek.co.jp
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakatani
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Seki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Chisato
authors.initials: C
authors.lastname: Taki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nishimura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takaki
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000818:Animals; D001681:Biological Assay; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000166:cytology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide