MAG-EPA and 17,18-EpETE target cytoplasmic signalling pathways to reduce short-term airway hyperresponsiveness

摘要: This study was aimed to investigate the role of eicosapentaenoic acid monoacylglyceride (MAG-EPA) and 17,18-epoxyeicosatetraenoic (17,18-EpETE) on regulation contractile reactivity nuclear protein expression in 72-h-cultured TNF-α-treated guinea pig tracheal rings. Tension measurements performed native tissues demonstrated that cytochrome P-450 epoxygenase (CYP450)-dependent EPA metabolite, 17,18-EpETE, displayed a higher potency than MAG-EPA inhibiting U-46619-induced tone. Calphostin C (a PKC inhibitor), whether association or not with had no further effect, while 17,18-EpETE Y-27632 Rho kinase inhibitor) yielded additive effects. Of note, pre-treatments normalized responses broncho-constrictive agents trachea. The enhanced TNF-α, P-p65-nuclear factor kappaB (NF)-κB, c-fos c-Jun likely contributed hyperresponsiveness. β-Escin-permeabilized preparations abolished Ca2+ hypersensitivity, suggesting blunting and/or activation. Lastly, activation NF-κB activating protein-1 (AP-1) signalling by exogenous TNF-α markedly increased response MCh, through an increase 17-kDa PKC-potentiated inhibitory PP1 (CPI-17) phosphorylation IκBα degradation. Dual incubation calphostin induced cumulative effects MCh TNF-α-incubated also reduced detection level P-p65-NF-κB AP-1 subunits. present data provide evidence MAG-EPA, its bioactive represents prospective pharmacological target respiratory diseases.