Submitted on July 21, 2008
Revised on March 23, 2009
Accepted on March 24, 2009
Lipoxin A4 inhibits IL-1
-induced IL-8 and ICAM-1 expression in 1321N1 human astrocytoma cells
Yann Decker1, Gethin McBean2, and Catherine Godson3*
1 Conway Institute
2 University College Dublin
3 UCD
* To whom correspondence should be addressed. E-mail: catherine.godson{at}ucd.ie.
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 pro-resolution effects on cells of myeloid and non myeloid 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 LXA4, 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-1
-induced stimulation of IL-8 and ICAM-1 mRNA expression in these cells. Furthermore, LXA4 (10 nM) decreased the expression of IL-1-induced IL-8 protein (p<0.05). LXA4 (10 nM) was found to inhibit IL-1-induced degradation of I
B
(p<0.05) and the activation of a 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.
