title: Water-soluble chitosan inhibits the production of pro-inflammatory cytokine in human astrocytoma cells activated by amyloid beta peptide and interleukin-1beta.
abstract: A chronic inflammatory response associated with beta-amyloid (Abeta) and interleukin-1beta (IL-1beta) is responsible for the pathology of Alzheimer's disease (AD). Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in AD. To investigate the biological effect of water-soluble chitosan (WSC), we examined cytotoxicity, production of pro-inflammatory cytokines and inducible nitric-oxide synthase (iNOS) on human astrocytoma cell line CCF-STTG1 stimulated with IL-1beta and Abeta fragment 25-35 (Abeta[25-35]). In 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide colorimetric assay, WSC by itself had no effect on cell viability on human astrocytoma cells. The effects of WSC on tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were evaluated with enzyme-linked immunosorbent assay and Western blotting. The production of TNF-alpha and IL-6 was induced by IL-1beta and Abeta[25-35] and synergistically amplified by the co-stimulation of IL-1beta and Abeta[25-35]. The secretion and expression of pro-inflammatory cytokines, TNF-alpha and IL-6, was significantly inhibited by pretreatment with WSC in human astrocytoma cells. The expression of iNOS was induced by IL-1beta and Abeta[25-35] and was partially inhibited by treatment with WSC. We demonstrate the regulatory effects of WSC in human astrocytes for the first time and suggest the anti-inflammatory effect of WSC may reduce and delay AD pathologic events.
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy and Korea Institute of Oriental Pharmacy, Wonkwang University, Iksan, Chonbuk 570-749, South Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Man-Joon
authors.initials: MJ
authors.lastname: Sung
authors.forename: Sang-Bong
authors.initials: SB
authors.lastname: Seo
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Yoo
authors.forename: Woon-Ki
authors.initials: WK
authors.lastname: Lim
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001254:Astrocytoma; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002686:Chitin / Q000031:analogs & derivatives / Q000494:pharmacology*; D048271:Chitosan; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D016229:Amyloid beta-Peptides; D002686:Chitin; D048271:Chitosan; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors