title: Inhibition of inducible nitric oxide synthase and interleukin-1β expression by tunicamycin in cultured glial cells exposed to lipopolysaccharide.
abstract: Endoplasmic reticulum (ER) stress has recently been implicated in human diseases such as Alzheimer׳s disease (AD) and Parkinson׳s disease (PD). However, the link between the immune system, ER stress, and the development of neurodegenerative diseases has not yet been clarified in detail. Mouse primary cultured astrocytes were treated with lipopolysaccharide (LPS) and/or tunicamycin (Tm), and inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β levels were then measured using RT-PCR, ELISA, and Western blotting. Activation of the immune system by LPS triggered inflammatory responses in astrocytes, as measured by the induction of iNOS and IL-1β. Tm-induced ER stress inhibited the LPS-induced expression of IL-1β and iNOS at the protein level. On the other hand, ER stress alone did not induce the expression of IL-1β or iNOS. The inhibitory effect of ER stress on iNOS and IL-1β may not be mediated transcriptionally as we did not observe inhibition at the mRNA level. LPS-induced iNOS protein levels were attenuated by the Tm post-treatment in the absence of LPS. Overall, these results suggest that ER stress negatively regulates the expression of IL-1β and iNOS in LPS-activated astrocytes.
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoi
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Noguchi
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Misae
authors.initials: M
authors.lastname: Takakuwa
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Miya
authors.initials: M
authors.lastname: Honda
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okuma
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Electronic address: ozawak@hiroshima-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D020126:Brefeldin A / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; C497250:Ddit3 protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D020126:Brefeldin A; D004533:Egtazic Acid; D052247:Nitric Oxide Synthase Type II; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
keywords: Astrocytes; Endoplasmic reticulum stress; Inducible nitric oxide synthase; Interleukin-1β