Inhibitory effect of high molecular weight water-soluble chitosan on hypoxia-induced inflammatory cytokine production.
Chitosan is widely used to treat patients with hypoxia-induced diseases such as ischemia, neuronal death, cerebral stroke, and cerebral infarction. Using the ELISA method, we examined the effect of high molecular weight water-soluble chitosan (WSC) on inflammatory cytokine production in the desferrioxamine (DFX, known to mimic hypoxia)-stimulated human mast cell line HMC-1. DFX significantly increased interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha production compared with the control in a time-dependent manner (p<0.05), but did not affect IL-1alpha production and mRNA expression. The increase in IL-6, IL-8, and TNF-alpha levels was significantly inhibited by WSC in a dose-dependent manner with IC(50) values of 0.77, 0.88, and 2.5 microg/ml, respectively. The maximal inhibition rate of IL-6, IL-8, and TNF-alpha production by WSC was 64+/-9.7%, 80+/-9.4% and 54+/-4.5%, respectively. In addition, WSC inhibited DFX-induced activation of nuclear factor (NF)-kappaB. In conclusion, these results suggest that WSC is an inhibitor of NF-kappaB under hypoxic conditions, which might explain its beneficial effect in the treatment of hypoxia-induced inflammatory diseases.
Seo
Sang-Bong
SB
Department of International Development Engineering, Tokyo Institute of Technology, Ookayama, Meguro-ku, Japan.
Jeong
Hyun-Ja
HJ
Chung
Hwan-Suck
HS
Lee
Joo-Don
JD
You
Yong-Ouk
YO
Kajiuchi
Toshio
T
Kim
Hyung-Min
HM
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D048271:Chitosan; D003124:Colorimetry; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014867:Water
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D002686:Chitin; D048271:Chitosan