Abstract
BackgroundPulmonary fibrosis is an untreatable, fatal disease characterized by excess deposition of extracellular matrix and inflammation. Although the etiology of pulmonary fibrosis is unknown, recent studies have implicated dysregulated immune responses and wound healing. Since n-3 polyunsaturated fatty acids (n-3 PUFAs) may beneficially modulate immune responses in a variety of inflammatory disorders, we investigated the therapeutic role of docosahexaenoic acid (DHA), a single n-3 PUFA, in lung fibrosis.MethodsIntratracheal DHA or PBS was administered to mouse lungs 4 days prior to intratracheal bleomycin treatment. Body weight and survival were monitored for 21 days. Bronchoalveolar fluid (BALF) and lung inflammatory cells, cytokines, eicosanoids, histology and lung function were determined on serial days (0, 3, 7, 14, 21) after bleomycin injury.ResultsIntratracheal administration of DHA mitigated bleomycin-induced lung injury. Mice pretreated with DHA had significantly less weight loss and mortality after bleomycin injury. The lungs from DHA-pretreated mice had markedly less fibrosis. DHA pretreatment also protected the mice from the functional changes associated with bleomycin injury. Bleomycin-induced cellular inflammation in BALF and lung tissue was blunted by DHA pretreatment. These advantageous effects of DHA pretreatment were associated with decreased IL-6, LTB4, PGE2 and increased IL-10.ConclusionsOur findings demonstrate that intratracheal administration of DHA, a single PUFA, protected mice from the development of bleomycin-induced pulmonary inflammation and fibrosis. These results suggest that further investigations regarding the role of n-3 polyunsaturated fatty acids in fibrotic lung injury and repair are needed.
Highlights
Pulmonary fibrosis is an untreatable, fatal disease characterized by excess deposition of extracellular matrix and inflammation
It is believed that the beneficial effects of n-3 polyunsaturated fatty acid (PUFA) are due in part to the replacement of arachidonic acid in the membrane phospholipids of inflammatory cells with the n-3 PUFAs leading to a reduced capacity of immune cells to synthesize LTs and PGs [36,37]
We demonstrate that docosahexaenoic acid (DHA), one best-known n-3 PUFA, protects mice from bleomycin-induced pulmonary inflammation and fibrosis
Summary
Pulmonary fibrosis is an untreatable, fatal disease characterized by excess deposition of extracellular matrix and inflammation. Since n-3 polyunsaturated fatty acids (n-3 PUFAs) may beneficially modulate immune responses in a variety of inflammatory disorders, we investigated the therapeutic role of docosahexaenoic acid (DHA), a single n-3 PUFA, in lung fibrosis. Investigating a single, pure polyunsaturated fatty acid (PUFA) is pivotal in understanding its role in diseases. Recent studies have showed that a pure n-3 PUFA may exert beneficial effects in inflammatory ailments [27,28,29,30,31]. Intratracheal DHA mitigated bleomycin induced mortality, weight loss, inflammation, histological damage and loss of lung function. Overall these findings provide insight into the disease process as well as suggest a novel therapeutic approach for pulmonary fibrosis
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