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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/C1420    most recent 00380.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Decker, Y. Articles by Godson, C. PubMed PubMed Citation Articles by Decker, Y. Articles by Godson, C.

NERVOUS SYSTEM CELL BIOLOGY

Lipoxin A₄ inhibits IL-1β-induced IL-8 and ICAM-1 expression in 1321N1 human astrocytoma cells

UCD School of Biomolecular and Biomedical Science¹ and UCD School of Medicine, Medical Science and Diabetes Research Centre², UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland

Submitted 21 July 2008 ; accepted in final form 24 March 2009

There is a growing appreciation that endogenously produced mediators may actively promote the resolution of inflammation. Lipoxins (LX) are a group of recently discovered lipid mediators that have been shown to exert anti-inflammatory and proresolution effects on cells of myeloid and nonmyeloid origin. LXs mediate a number of processes, including regression of pro-inflammatory cytokine production, inhibition of cell proliferation, and stimulation of phagocytosis of apoptotic leukocytes by macrophages. Lipoxin A₄ (LXA₄) is one of the principal LXs formed by mammalian cells. Recently, a G protein-coupled receptor that binds LXA_4, the lipoxin A₄ receptor, was identified in astrocytes and microglia, suggesting that these cells may be a target for LX action in the brain. In this study, we have investigated the potential of LXA₄ to modify inflammatory responses of astrocytes, using the 1321N1 human astrocytoma cell line as a model system. As shown by quantitative RT-PCR, LXA₄ (10 nM) significantly inhibited (P < 0.05) the IL-1β-induced stimulation of IL-8 and ICAM-1 expression in these cells. Furthermore, LXA₄ (10 nM) decreased the expression of IL-1β-induced IL-8 protein levels (P < 0.05). LXA₄ (10 nM) was found to inhibit IL-1β-induced degradation of IB (P < 0.05), and the activation of an NFB regulated reporter gene construct (P < 0.05). Overall, these data suggest that LXA₄ exerts anti-inflammatory effects in 1321N1 astrocytoma cells at least in part via an NFB-dependent mechanism. It is concluded that LXA₄ may represent a potentially novel therapeutic approach to acute or chronic inflammation in the brain.

neuroinflammation; formyl-peptide receptor like-1; alxr