Novel biphasic role of resolvin D1 on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts is partly through PI3K/AKT and ERK2 pathways.

Fibroblasts, far from being merely bystander cells, are known to play a specific role in inflammation resolution after an acute injury. As the endogenous "braking signal," resolvins possess potent anti-inflammatory and pro-resolution actions. We demonstrated that the expression of COX-2 protein was significantly peaked initially at 6 hours but then also at 48 hours after LPS stimulation in lung fibroblasts. PGE2 levels also peaked at 6 hours, and PGD2 levels were increased and peaked at 48 hours. However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts. Exogenous resolvin D1 inhibited the first peak of COX-2 expression as well as the production of PGE2 induced by LPS. In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2 induced by LPS. In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.