Recent both epidemiologic and experimental results evidenced a strong correlation between inflammation process and cancer induction. The inflammation effect seems to be due to the production of oxygen and nitrogen radicals, and of growth-promoting cytokines, to the inhibition of tumour suppressor and to the stimulation of signal transduction pathways leading to cell proliferation. This correlation was confirmed by the observation that agents modulating the production of molecular mediators of inflammation possess anti-carcinogenic activity. In turn, tumour induces in host a chronic inflammation status. In physiological conditions, n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs possess opposite influence upon inflammatory processes: n-6 PUFAs induce it, whereas n-3 decrease it. Since both PUFAs n-3 and n-6 are taken via diet in different amount, the objective of this research was to determine whether different n-3/n-6 PUFA ratios affect lipopolysaccharide (LPS)-induced cytokine release in human lung A549 cells. Docosahexaenoic acid (DHA, n-3) plus arachidonic acid (AA, n-6) in four different n-3/n-6 ratios (1:1, 1:2, 1:4 and 1:7) were added to A549 cells 3 hours after LPS administration. Both pro- (TNF-alpha, IL-6 and IL-8) and anti-inflammatory (IL-10) cytokine levels were measured in culture media after further 4 hours. The release of pro-inflammatory cytokines was reduced by 1:1 and 1:2 n-3/n-6 ratios, but increased by 1:4 and 1:7 n-3/n-6 ratios. Moreover, the 1:1 and 1:2 n-3/n-6 ratios increased the release of IL-10 (p<0.001) more than other ratios tested. The results of this study firstly evidenced that pro-inflammatory cytokine release is reduced by increasing the n-3 share in n-3/n-6 PUFA ratio, whereas after the administration of an n-6 predominance is increased. These results support the biochemical basis to shift the dietary PUFA uptake from n-6 to n-3 in order to prevent the induction of cancer. Moreover, they can also represent an important starting point to shift the PUFA content from n-6 to n-3 in nutritional supports for neoplastic patients.
N-3/n-6 polyunsaturated fatty acid ratios differently affect cytokine release in human lung cells
MUZIO, Giuliana;MAGGIORA, Marina;CANUTO, Rosa Angela
2010-01-01
Abstract
Recent both epidemiologic and experimental results evidenced a strong correlation between inflammation process and cancer induction. The inflammation effect seems to be due to the production of oxygen and nitrogen radicals, and of growth-promoting cytokines, to the inhibition of tumour suppressor and to the stimulation of signal transduction pathways leading to cell proliferation. This correlation was confirmed by the observation that agents modulating the production of molecular mediators of inflammation possess anti-carcinogenic activity. In turn, tumour induces in host a chronic inflammation status. In physiological conditions, n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs possess opposite influence upon inflammatory processes: n-6 PUFAs induce it, whereas n-3 decrease it. Since both PUFAs n-3 and n-6 are taken via diet in different amount, the objective of this research was to determine whether different n-3/n-6 PUFA ratios affect lipopolysaccharide (LPS)-induced cytokine release in human lung A549 cells. Docosahexaenoic acid (DHA, n-3) plus arachidonic acid (AA, n-6) in four different n-3/n-6 ratios (1:1, 1:2, 1:4 and 1:7) were added to A549 cells 3 hours after LPS administration. Both pro- (TNF-alpha, IL-6 and IL-8) and anti-inflammatory (IL-10) cytokine levels were measured in culture media after further 4 hours. The release of pro-inflammatory cytokines was reduced by 1:1 and 1:2 n-3/n-6 ratios, but increased by 1:4 and 1:7 n-3/n-6 ratios. Moreover, the 1:1 and 1:2 n-3/n-6 ratios increased the release of IL-10 (p<0.001) more than other ratios tested. The results of this study firstly evidenced that pro-inflammatory cytokine release is reduced by increasing the n-3 share in n-3/n-6 PUFA ratio, whereas after the administration of an n-6 predominance is increased. These results support the biochemical basis to shift the dietary PUFA uptake from n-6 to n-3 in order to prevent the induction of cancer. Moreover, they can also represent an important starting point to shift the PUFA content from n-6 to n-3 in nutritional supports for neoplastic patients.
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