title: Amphotericin B Increases Transglutaminase 2 Expression Associated with Upregulation of Endocytotic Activity in Mouse Microglial Cell Line BV-2.
abstract: Amphotericin B (AmB), a polyene antibiotic, is reported to cause the microglial activation to induce nitric oxide (NO) production and proinflammatory cytokines expression, and change neurotrophic factors expression in cultured microglia (Motoyoshi et al. in Neurochem Int 52:1290-1296, 2008). On the other hand, tissue-type transglutaminase (TG2) is involved in connection to phagocytes with apoptotic cells. Engulfment of neurons by activated microglia is thought to cause neurodegenerative diseases but detail is unclear, and involvement of TG2 in phagocytosis has been reported in our previous study using lipopolysaccharide-stimulated BV-2 cells (Kawabe et al. in Neuroimmunomodulation 22(4):243-249, 2015). In the present study, we examined the changes of TG2 expression, phagocytosis and pinocytosis in BV-2 cells stimulated by AmB. AmB stimulation increased TG2 expression and TG activity. Phagocytosis of dead cells and pinocytosis of fluorescent microbeads were also up-regulated by AmB stimulation in BV-2 cells. Blockade of TG activity by cystamine, an inhibitor of TGs, suppressed AmB-enhanced TG2 expression, TG activity, NO production, phagocytosis and pinocytosis. Excessive NO production from microglia and/or facilitation of phagocytosis might be involved in neuronal death. To control TG activity might make possible to protect neurons and care for CNS diseases.
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabe
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan. takano@vet.osakafu-u.ac.jp.
authors.forename: Katsura
authors.initials: K
authors.lastname: Takano
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Moriyama
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000666:Amphotericin B; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Amphotericin B; BV-2; Cystamine; Endocytosis; Microglia; Transglutaminase 2