Figure 7

Schematic representation of the suppressive effect of 15-LOX metabolites on MMP-1/MMP-13 expression. Pro-inflammatory cytokines such as IL-1 interact with their respective receptors that activate MAPK signalling and downstream transcription factors, resulting in the transcription of MMP-1 and MMP-13 genes. 15-LOX convert AA and LA to 15-HETE and 13-HODE, which then activate PPARγ. Activated PPARγ antagonizes the transcriptional activity of AP-1, NF-κB and PEA3, which results in the inhibition of the expression of their target genes (for instance, MMP-1 and MMP-13). AA, arachidonic acid; AP, activator protein; HETE, hydroxyeicosatetraenoic acid; HODE, hydroxy octadecadienoic acid; LA, linoeic acid; LOX, lipoxygenase; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; NF-κB, nuclear factor-κB; PEA3, Polyoma Enhancer Activator 3; PPAR, peroxisome proliferator-activated receptor.