Aspirin-triggered lipoxin A4 attenuates lipopolysaccharide induced inflammatory response in primary astrocytes

The activation of astrocytes contributes to inflammatory responses underlying brain injury and neurodegenerative diseases. Lipoxins have emerged as mediators of endogenous anti-inflammatory events. However, the involvement of aspirin-triggered-lipoxin A(4) (ATL) in astrocyte-induced neuroinflammatory responses has not been investigated. Here, we examined the anti-inflammatory effects of ATL in the central nervous system using rat astrocyte cultures stimulated with lipopolysaccharide (LPS). We found that pretreatment with ATL exerted potent anti-inflammatory effects by inhibiting LPS-induced production of nitric oxide and prostaglandin E-2. ATL also reduced the expression of cyclooxygenase 2 and inducible nitric oxide synthase mRNA and protein. Furthermore, ATL suppressed the LPS-induced translocation of the NF-kappa B p65 subunit to the nucleus and prevented LPS-induced I kappa B alpha phosphorylation in a dose-dependent manner. These findings suggest that ATL attenuates neuroinflammation by inhibiting the NF-kappa B signal transducer pathway in cultured cortical astrocytes. (C) 2013 Elsevier B.V. All rights reserved.