＜正＞ Background Lipoxins （LXs）,endogenous anti-inflammatory and pro-resolving eicosanoids generated during variousinflammatory conditions,have novel immunomodulatory properties.Because dendritic cells （DCs） play crucial roles in theinitiation and maintenance of immune response,we determined whether LXs could modulate the maturation process ofDCs and investigated the effects of lipoxin A4 （LXA4） on lipopolysaccharide （LPS）-induced differentiation of RAW264.7cells into dendritic-like cells.Methods RAW264.7 cells were cultured in vitro with 1 μg/ml LPS in the absence or presence of LXA4 for 24 hours,andcellular surface markers （MHC-Ⅱ,CD80 （B7-1）,CD86（B7-2）） were measured by flow cytometry （FCM）.Mixedlymphocyte reaction was performed to evaluate the allostimulatory activity.Cytoplastic IKB degradation and nuclear factorkappa B （NF-κB） translocation were detected by Western blotting.Luciferase reporter plasmid was transiently transfectedinto RAW264.7 cells,and luciferase activity was determined to measure the transcriptional activity of NF-κB.Results LXA4 reduced the ratio of LPS-treated RAW264.7 cells to DCs with morphological characteristics and inhibitedthe expression of MHC Ⅱ.LPS-induced up-regulation of CD86 was moderately suppressed by LXA4 but no obviouschange of CD80 was observed.Moreover,LXA4 weakened the allostimulatory activity of LPS-treated RAW264.7 cells.These alterations of LPS+LXA4-treated cells were associated with a marked inhibition of IκB degradation,NF-κBtranslocation and then the transcriptional activity of NF-κB.Conclusions LXA4 negatively regulates LPS-induced differentiation of RAW264.7 cells into dendritic-like cells.Thisactivity reveals an undescribed mechanism of LXA4 to prevent excessive and sustained immune reaction by regulatingmaturation of DCs.
展开▼
