A study on the anti-inflammatory activity of brown alga Sargassum siliquastrum led to the isolation of sargachromanol G (SG). In this study, the anti-inflammatory effect and the action mechanism of SG have been investigated in murine macrophage cell line RAW 264.7. SG dosedependently inhibited the production of inflammatory markers [nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E(2) (PGE(2)), and cyclooxygenase-2 (COX-2)] and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6] induced by LPS treatment. To further elucidate the mechanism of this inhibitory effect of SG, we studied LPS-induced nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinases (MAPKs) phosphorylation. SG inhibited the phosphorylation IκB-α and NF-κB (p65 and p50) and MAPK (ERK1/2, JNK, and p38) in a dose dependent manner. These results suggest that the anti-inflammatory activity of SG results from its modulation of pro-inflammatory cytokines and mediators via the suppression of NF-κB activation and MAPK phosphorylation.

Regulatory T cells (Tregs) have key roles in the immune response by suppressing the differentiation and proliferation of various immune cells. The beneficial effects of docosahexaenoic acid (DHA) have been described for many diseases; however, the mechanism by which it modulates the immune system is poorly understood. Therefore, the aim of this study was to examine whether DHA suppresses allergic reactions and upregulates the generation of CD4(+)Foxp3(+) T cells. We also examined the effects of transfusing interleukin-10/transforming growth factor-β (TGF-β)-modified macrophages (M2 macrophages) treated with DHA into a mouse model of atopic dermatitis. Here, we show that administration of DHA upregulates the generation of TGF-β-dependent CD4(+) forkhead box protein 3 (Foxp3(+)) Tregs. DHA induced T-cell hypo-responsiveness and downregulated cytokines associated with T helper (Th)-1, Th2, and Th17 cells. The differentiation of Foxp3(+) Tregs into CD4(+) T cells was directly mediated by DHA-M2 macrophages, which deactivated effector macrophages and inhibited CD4(+) T-cell proliferation. DHA showed therapeutic effects in mice with experimental atopic dermatitis. These results show that DHA enhances the function of M2 macrophages and that the generation of Tregs effectively protects mice against an inflammatory immune disorder. Thus, DHA may be a useful therapeutic strategy for treating chronic inflammatory diseases.

BackgroundAllergic skin inflammation such as atopic dermatitis (AD), which is characterized by pruritus and inflammation, is regulated partly through the activity of regulatory T cells (Tregs). Tregs play key roles in the immune response by preventing or suppressing the differentiation, proliferation and function of various immune cells, including CD4+ T cells. Recent studies report that fermentation has a tremendous capacity to transform chemical structures or create new substances, and the omega-3 polyunsaturated fatty acids (n-3 PUFAs) in fish oil can reduce inflammation in allergic patients. The beneficial effects of natural fish oil (NFO) have been described in many diseases, but the mechanism by which fermented fish oil (FFO) modulates the immune system and the allergic response is poorly understood. In this study, we produced FFO and tested its ability to suppress the allergic inflammatory response and to activate CD4+CD25+Foxp3+ Tregs.ResultsThe ability of FFO and NFO to modulate the immune system was investigated using a mouse model of AD. Administration of FFO or NFO in the drinking water alleviated the allergic inflammation in the skin, and FFO was more effective than NFO. FFO treatment did increase the expression of the immune-suppressive cytokines TGF-β and IL-10. In addition, ingestion of FFO increased Foxp3 expression and the number of CD4+CD25+Foxp3+ Tregs compared with NFO.ConclusionsThese results suggest that the anti-allergic effect of FFO is associated with enrichment of CD4+CD25+ Foxp3+ T cells at the inflamed sites and that FFO may be effective in treating the allergic symptoms of AD.

Background Dietary Mg intake is associated with a decreased risk of developing heart failure, whereas low circulating Mg level is associated with increased cardiovascular mortality. We investigated whether Mg deficiency alone could cause cardiomyopathy. Methods and Results C57BL/6J mice were fed with a low Mg (low‐Mg, 15–30 mg/kg Mg) or a normal Mg (nl‐Mg, 600 mg/kg Mg) diet for 6 weeks. To test reversibility, half of the low‐Mg mice were fed then with nl‐Mg diet for another 6 weeks. Low‐Mg diet significantly decreased mouse serum Mg (0.38±0.03 versus 1.14±0.03 mmol/L for nl‐Mg; P <0.0001) with a reciprocal increase in serum Ca, K, and Na. Low‐Mg mice exhibited impaired cardiac relaxation (ratio between mitral peak early filling velocity E and longitudinal tissue velocity of the mitral anterior annulus e, 21.1±1.1 versus 15.4±0.4 for nl‐Mg; P =0.011). Cellular ATP was decreased significantly in low‐Mg hearts. The changes were accompanied by mitochondrial dysfunction with mitochondrial reactive oxygen species overproduction and membrane depolarization. cMyBPC (cardiac myosin‐binding protein C) was S ‐glutathionylated in low‐Mg mouse hearts. All these changes were normalized with Mg repletion. In vivo (2‐(2,2,6,6‐tetramethylpiperidin‐1‐oxyl‐4‐ylamino)‐2‐oxoethyl)triphenylphosphonium chloride treatment during low‐Mg diet improved cardiac relaxation, increased ATP levels, and reduced S ‐glutathionylated cMyBPC. Conclusions Mg deficiency caused a reversible diastolic cardiomyopathy associated with mitochondrial dysfunction and oxidative modification of cMyBPC. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure.