title: The Omega-3 Fatty Acid Docosahexaenoic Acid Modulates Inflammatory Mediator Release in Human Alveolar Cells Exposed to Bronchoalveolar Lavage Fluid of ARDS Patients.
abstract: BACKGROUND
  This study investigated whether the 1 : 2 ω-3/ω-6 ratio may reduce proinflammatory response in human alveolar cells (A549) exposed to an ex vivo inflammatory stimulus (bronchoalveolar lavage fluid (BALF) of acute respiratory distress syndrome (ARDS) patients). Methods. We exposed A549 cells to the BALF collected from 12 ARDS patients. After 18 hours, fatty acids (FA) were added as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in two ratios (1 : 2 or 1 : 7). 24 hours later, in culture supernatants were evaluated cytokines (TNF-α, IL-6, IL-8, and IL-10) and prostaglandins (PGE2 and PGE3) release. The FA percentage content in A549 membrane phospholipids, content of COX-2, level of PPARγ, and NF-κB binding activity were determined.
  
  
  RESULTS
  The 1 : 2 DHA/AA ratio reversed the baseline predominance of ω-6 over ω-3 in the cell membranes (P < 0.001). The proinflammatory cytokine release was reduced by the 1 : 2 ratio (P < 0.01 to <0.001) but was increased by the 1 : 7 ratio (P < 0.01). The 1 : 2 ratio reduced COX-2 and PGE2 (P < 0.001) as well as NF-κB translocation into the nucleus (P < 0.01), while it increased activation of PPARγ and IL-10 release (P < 0.001). Conclusion. This study demonstrated that shifting the FA supply from ω-6 to ω-3 decreased proinflammatory mediator release in human alveolar cells exposed to BALF of ARDS patients.
authors: Anesthesiology and Intensive Care, Department of Medicine, S. Giovanni Battista Hospital, University of Turin, Via A.M. Dogliotti 14, 10126 Turin, Italy.
authors: Paolo
authors: P
authors: Cotogni
authors: Department of Medical Sciences, University of Turin, Via A.M. Dogliotti 14, 10126 Turin, Italy.
authors: Antonella
authors: A
authors: Trombetta
authors: Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.
authors: Giuliana
authors: G
authors: Muzio
authors: Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.
authors: Marina
authors: M
authors: Maggiora
authors: Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.
authors: Rosa Angela
authors: RA
authors: Canuto
mesh_terms: D016718:Arachidonic Acid / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000737:chemistry / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D047495:PPAR gamma / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D018836:Inflammation Mediators; D016328:NF-kappa B; D047495:PPAR gamma; D016753:Interleukin-10; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone