Chondroitin sulfate inhibits lipopolysaccharide-induced inflammation in rat astrocytes by preventing nuclear factor kappa B activation.
Chondroitin sulfate (CS) is a glucosaminoglycan (GAG) currently used for the treatment of osteoarthritis because of its antiinflammatory and antiapoptotic actions. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the CNS. Since neuroinflammation has been implicated in different neuronal pathologies, this study was planned to investigate how CS could modulate the inflammatory response in the CNS by using rat astrocyte cultures stimulated with lipopolysaccharide (LPS). We have evaluated different proteins implicated in the nuclear factor kappa B (NFkappaB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways employing RT-PCR, western blot and immunofluorescence techniques. At 10 microM, CS prevented translocation of p65 to the nucleus, reduced tumour necrosis factor alpha (TNF-alpha) mRNA and mitigated cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) induction by LPS. However, it did not modify LPS-induced IP-10 and SOCS-1 mRNA, proteins that participate in the JAK/STAT pathway. The results of this study indicate that CS can potentially reduce neuroinflammation by inhibition of NFkappaB. Therefore endogenous GAGs could afford neuroimmunomodulatory actions under neurotoxic conditions.
Cañas
N
N
Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Gorina
R
R
Planas
A M
AM
Vergés
J
J
Montell
E
E
García
A G
AG
López
M G
MG
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005911:Gliosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D053613:Janus Kinase 1 / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050791:STAT Transcription Factors / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C498145:Rela protein, rat; D050791:STAT Transcription Factors; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D002809:Chondroitin Sulfates; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C507906:Jak1 protein, rat; D053613:Janus Kinase 1