Sphingosine 1-phosphate Increases COX-2 Expression and PGE2 Secretion: Effects on β2-adrenergic Receptor Desensitization.

Sphingosine 1-phosphate Increases COX-2 Expression and PGE2 Secretion: Effects on β2-adrenergic Receptor Desensitization. Am J Respir Cell Mol Biol. 2015 Jun 22; Authors: Rumzhum NN, Rahman MM, Oliver BG, Ammit AJ Abstract Tachyphylaxis of the β2-adrenergic receptor limits the efficacy of bronchodilatory β2-agonists in respiratory disease. Cellular studies in airway smooth muscle (ASM) have shown that inflammatory mediators and infectious stimuli reduce β2-adrenergic responsiveness in a cyclooxygenase 2 (COX-2)-mediated, prostaglandin E2 (PGE2)-dependant manner. Herein we show that sphingosine 1-phosphate (S1P), a bioactive sphingolipid that plays an important role in pathophysiology of asthma, also induces β2-adrenergic receptor desensitization in bronchial ASM cells and exerts hyporesponsiveness to β2-agonist. We treated ASM cells with S1P (1 μM) for up to 24 h and then examined the temporal kinetics of COX-2 mRNA expression, protein upregulation and PGE2 secretion. S1P significantly enhanced COX-2 expression and PGE2 secretion and this was repressed by the selective COX-2 inhibitor, celecoxib, the corticosteroid dexamethasone, or siRNA knockdown of COX-2 expression. In combination with another pro-inflammatory mediator found elevated in asthmatic airways, the cytokine tumour necrosis factor α (TNFα), we observed that S1P-induced COX-2 mRNA expression and protein upregulation and PGE2 secretion from ASM cells were signific...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research