resolvin-d1 and Bronchitis

The aim of this study was to investigate the effects of resolvin D1 (RvD1), as well as the combined treatment of docosahexaenoic acid monoglyceride (MAG-DHA) and acetylsalicylic acid (ASA), on the resolution of inflammation markers and Ca(2+) sensitivity in IL-13-pretreated human bronchi (HB). Tension measurements performed with 300 nM RvD1 largely abolished (50%) the over-reactivity triggered by 10 ng/ml IL-13 pretreatment and reversed hyper Ca(2+) sensitivity. Addition of 300 nM 17(S)-HpDoHE, the metabolic intermediate between DHA and RvD1, displayed similar effects. In the presence of 100 μM ASA (a COX inhibitor), the inhibitory effect of 1 μM MAG-DHA on muscarinic tone was further amplified, but not in the presence of Ibuprofen. Western blot analysis revealed that the combined treatment of MAG-DHA and ASA upregulated GPR-32 expression and downregulated cytosolic TNFα detection, hence preventing IκBα degradation and p65-NFκB phosphorylation. The Ca(2+) sensitivity of HB was also quantified on β-escin permeabilized preparations. The presence of ASA potentiated the inhibitory effects of MAG-DHA in reducing the Ca(2+) hypersensitivity triggered by IL-13 by decreasing the phosphorylation levels of the PKC-potentiated inhibitor protein-17 regulatory protein (CPI-17). In summary, MAG-DHA combined with ASA, as well as exogenously added RvD1, may represent valuable assets against critical AHR disorder.

Topics: Airway Resistance; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bronchi; Bronchitis; Bronchodilator Agents; Calcium Signaling; Cyclooxygenase Inhibitors; Docosahexaenoic Acids; Drug Synergism; Fatty Acids, Omega-3; Humans; I-kappa B Kinase; In Vitro Techniques; Interleukin-13; Intracellular Signaling Peptides and Proteins; Monoglycerides; Muscle Proteins; Phosphoprotein Phosphatases; Phosphorylation; Protein Processing, Post-Translational; Receptors, G-Protein-Coupled; Transcription Factor RelA; Tumor Necrosis Factor-alpha