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The Omega-3 Fatty Acid Docosahexaenoic Acid Modulates Inflammatory Mediator Release in Human Alveolar Cells Exposed to Bronchoalveolar Lavage Fluid of ARDS Patients.

Cotogni P, Trombetta A, Muzio G, Maggiora M, Canuto RA - Biomed Res Int (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Anesthesiology and Intensive Care, Department of Medicine, S. Giovanni Battista Hospital, University of Turin, Via A.M. Dogliotti 14, 10126 Turin, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of ω-3/ω-6 PUFA ratios on the percentage content of AA and DHA in A549 membrane phospholipids. Relative percentage content of AA (white bars) and DHA (black bars) in phospholipids of A549 cell membranes stimulated with BALF and treated with 50 μM 1 : 2 or 1 : 7 DHA/AA PUFA ratios. Data are presented as percentage content of AA and DHA in the membrane phospholipids of unstimulated or stimulated A549 cells as indicated. Data are presented as mean ± standard deviation of 4 independent experiments (n = 4). PUFA, polyunsaturated fatty acid; AA, arachidonic acid; DHA, docosahexaenoic acid; BALF, bronchoalveolar lavage fluid. ***P < 0.001 BALF versus unstimulated. **P < 0.01 1 : 2 and 1 : 7 DHA/AA versus all. ###P < 0.001 versus all.
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fig4: Effects of ω-3/ω-6 PUFA ratios on the percentage content of AA and DHA in A549 membrane phospholipids. Relative percentage content of AA (white bars) and DHA (black bars) in phospholipids of A549 cell membranes stimulated with BALF and treated with 50 μM 1 : 2 or 1 : 7 DHA/AA PUFA ratios. Data are presented as percentage content of AA and DHA in the membrane phospholipids of unstimulated or stimulated A549 cells as indicated. Data are presented as mean ± standard deviation of 4 independent experiments (n = 4). PUFA, polyunsaturated fatty acid; AA, arachidonic acid; DHA, docosahexaenoic acid; BALF, bronchoalveolar lavage fluid. ***P < 0.001 BALF versus unstimulated. **P < 0.01 1 : 2 and 1 : 7 DHA/AA versus all. ###P < 0.001 versus all.

Mentions: In our previous study, we demonstrated that at the baseline the ω-3/ω-6 PUFA ratio in membrane phospholipids of A549 was 1 : 5 and that it can be changed by challenging the cells with 1 : 1 or 1 : 2 DHA/AA ratios [32]. Here, we examined the DHA and AA content in membrane phospholipids of A549 BALF-stimulated and challenged with 1 : 2 or 1 : 7 ratios DHA/AA (Figure 4). At baseline in A549 membrane phospholipids the ω-6 PUFA fraction is predominant, with a ω-3/ω-6 ratio of 1 : 5. Notably, cell treatment with both DHA/AA ratios reduced the AA content in A549 membrane phospholipids, but the 1 : 2 DHA/AA ratio also significantly increased the DHA percentage content. The supply of 1 : 2 DHA/AA ratio reversed the baseline predominance of ω-6 over ω-3 in the ω-3/ω-6 PUFA ratio in membrane phospholipids of A549 cells.


The Omega-3 Fatty Acid Docosahexaenoic Acid Modulates Inflammatory Mediator Release in Human Alveolar Cells Exposed to Bronchoalveolar Lavage Fluid of ARDS Patients.

Cotogni P, Trombetta A, Muzio G, Maggiora M, Canuto RA - Biomed Res Int (2015)

Effects of ω-3/ω-6 PUFA ratios on the percentage content of AA and DHA in A549 membrane phospholipids. Relative percentage content of AA (white bars) and DHA (black bars) in phospholipids of A549 cell membranes stimulated with BALF and treated with 50 μM 1 : 2 or 1 : 7 DHA/AA PUFA ratios. Data are presented as percentage content of AA and DHA in the membrane phospholipids of unstimulated or stimulated A549 cells as indicated. Data are presented as mean ± standard deviation of 4 independent experiments (n = 4). PUFA, polyunsaturated fatty acid; AA, arachidonic acid; DHA, docosahexaenoic acid; BALF, bronchoalveolar lavage fluid. ***P < 0.001 BALF versus unstimulated. **P < 0.01 1 : 2 and 1 : 7 DHA/AA versus all. ###P < 0.001 versus all.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4537738&req=5

fig4: Effects of ω-3/ω-6 PUFA ratios on the percentage content of AA and DHA in A549 membrane phospholipids. Relative percentage content of AA (white bars) and DHA (black bars) in phospholipids of A549 cell membranes stimulated with BALF and treated with 50 μM 1 : 2 or 1 : 7 DHA/AA PUFA ratios. Data are presented as percentage content of AA and DHA in the membrane phospholipids of unstimulated or stimulated A549 cells as indicated. Data are presented as mean ± standard deviation of 4 independent experiments (n = 4). PUFA, polyunsaturated fatty acid; AA, arachidonic acid; DHA, docosahexaenoic acid; BALF, bronchoalveolar lavage fluid. ***P < 0.001 BALF versus unstimulated. **P < 0.01 1 : 2 and 1 : 7 DHA/AA versus all. ###P < 0.001 versus all.
Mentions: In our previous study, we demonstrated that at the baseline the ω-3/ω-6 PUFA ratio in membrane phospholipids of A549 was 1 : 5 and that it can be changed by challenging the cells with 1 : 1 or 1 : 2 DHA/AA ratios [32]. Here, we examined the DHA and AA content in membrane phospholipids of A549 BALF-stimulated and challenged with 1 : 2 or 1 : 7 ratios DHA/AA (Figure 4). At baseline in A549 membrane phospholipids the ω-6 PUFA fraction is predominant, with a ω-3/ω-6 ratio of 1 : 5. Notably, cell treatment with both DHA/AA ratios reduced the AA content in A549 membrane phospholipids, but the 1 : 2 DHA/AA ratio also significantly increased the DHA percentage content. The supply of 1 : 2 DHA/AA ratio reversed the baseline predominance of ω-6 over ω-3 in the ω-3/ω-6 PUFA ratio in membrane phospholipids of A549 cells.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Anesthesiology and Intensive Care, Department of Medicine, S. Giovanni Battista Hospital, University of Turin, Via A.M. Dogliotti 14, 10126 Turin, Italy.

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.

No MeSH data available.


Related in: MedlinePlus