Chondroitin sulfate inhibits lipopolysaccharide-induced inflammation in rat astrocytes by preventing nuclear factor kappa B activation

et al.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 (NFK{green}) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways employing RT-PCR, western blot and immunofluorescence techniques. At 10 μM, CS prevented translocation of p65 to the nucleus, reduced tumour necrosis factor alpha (TNF-α) 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 NFK{green}B. Therefore endogenous GAGs could afford neuroimmunomodulatory actions under neurotoxic conditions. © 2010 IBRO.This work was supported by “Cátedra Bioibérica/UAM de Inflamación Crónica y Citoprotección”(CABICYC) Spain and, in part by the Spanish Ministry of Science and Innovation Ref. SAF2009-12150 to MGL, SAF2008-04515-C02-01 to AMP, the Spanish Ministry of Health (Instituto de Salud Carlos III) RETICS-RD06/0026, Comunidad Autónoma de Madrid SAL2006/0275, Fundación CIEN, IS Carlos III, MICINN, N° PI016/09 and Agencia Lain Entralgo, CN N° NDE07/09, Comunidad de Madrid, Spain to AGG.Peer Reviewe