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Am J Physiol Cell Physiol. 2009 Jun;296(6):C1420-7. doi: 10.1152/ajpcell.00380.2008. Epub 2009 Apr 8.

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

Author information

1
UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

Abstract

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 A(4) (LXA(4)) is one of the principal LXs formed by mammalian cells. Recently, a G protein-coupled receptor that binds LXA(4,) the lipoxin A(4) 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 LXA(4) to modify inflammatory responses of astrocytes, using the 1321N1 human astrocytoma cell line as a model system. As shown by quantitative RT-PCR, LXA(4) (10 nM) significantly inhibited (P < 0.05) the IL-1beta-induced stimulation of IL-8 and ICAM-1 expression in these cells. Furthermore, LXA(4) (10 nM) decreased the expression of IL-1beta-induced IL-8 protein levels (P < 0.05). LXA(4) (10 nM) was found to inhibit IL-1beta-induced degradation of IkappaBalpha (P < 0.05), and the activation of an NFkappaB regulated reporter gene construct (P < 0.05). Overall, these data suggest that LXA(4) exerts anti-inflammatory effects in 1321N1 astrocytoma cells at least in part via an NFkappaB-dependent mechanism. It is concluded that LXA(4) may represent a potentially novel therapeutic approach to acute or chronic inflammation in the brain.

PMID:
19357230
DOI:
10.1152/ajpcell.00380.2008
[Indexed for MEDLINE]
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