Molecular mechanisms of immunosuppressive effects of dietary n-3 pufa, curcumin and limonin on murine cd4+ t cells

The molecular mechanisms of putative anti-inflammatory nutrients, i.e., fish oil, curcumin and limonin, were investgated with respect to CD4+ T cell function. Initially, using a DO11.10 mouse model which exhibits a transgenic T cell receptor specific to OVA 323-339 peptide, we demonstrated that dietary fish oil suppresses antigen-specific Th1 clonal expansion in vivo. Following immunization, the accumulation of adoptively transferred transgenic cells in wild type recipient mouse lymph nodes was suppressed. In addition, cell division analysis by carboxyfluorescein succinimidyl ester (CFSE) revealed that both total cell number in lymph nodes as well as cell division were decreased by fish oil. Since n-3 polyunsaturated fatty acids (PUFA), active long chain fatty acids in fish oil, elicit favorable effects on a variety of cell types, e.g., anti-tumor effect on colonocytes, amelioration of coronary heart disease and anti-inflammatory effects involving T cells, B cells, dendritic cells and macrophages, we postulated that a fundamental mechanism of action may explain the multiple effects observed. In a series of experiments described herein, we demonstrated that n-3 PUFA alters the formation/location of membrane subdomains, referenced to as lipid rafts. Specifically, lipid raft formation at the immunological synapse (IS) in CD4+ T cells was suppressed following membrane enrichment with n-3 PUFA. The alteration of lipid rafts down-regulated the localization of select signaling proteins, including F-actin, PKC and PLC-1, and phosphorylation of PLC-1 at the IS. Consequently, CD4+ T cell proliferation was suppressed as assessed by CFSE analysis and radioactive thymidine incorporation. Phytochemicals have been used for chemopreventive and chemotherapeutic purposes. We examined the putative anti-inflammatory effects of curcumin (1%) and limonin (0.02%) with respect to CD4+ T cell function. Dietary curcumin and limonin suppressed NF-B activation in CD4+ T cells. In addition, CD4+ T cell proliferation was modulated by 2% curcumin. We further investigated the combined therapeutic potential of phytochemicals and fish oil, containing n-3 PUFA. Interestingly, fish oil and limonin together significantly (P<0.05) suppressed T cell proliferation, whereas feeding either fish oil or limonin alone showed little effect. In summary, our data indicated that dietary fish oil alters proximal signaling of T cells by perturbing lipid raft formation. Curcumin and limoin are capable of suppressing NF-B in T cells, thereby exhibiting a synergistic effect when combined with fish oil. Further studies are required to elucidate the relationship of dietary dose of active compoments with respect to mechanism of actions

Characterization of cationic dextrin prepared by ultra high pressure (UHP)-assisted cationization reaction

AbstractCationic dextrins were prepared through substitution reaction of dextrin with low and high addition levels of 2,3-epoxypropyltrimethylammonium chloride (ETMAC), respectively. Conventional cationization reactions were carried out for 5h under continued stirring. UHP-assisted cationization reactions were conducted at three pressurization levels of 100, 300 and 500MPa for a pressure holding time of 30min. Degree of substitution (DS) of UHP-assisted cationic dextrins ranged from 0.58 to 1.51, and in general, their DS values were enhanced with increasing pressure levels. FT-IR and 13C NMR spectra indicated the presence of CN bond, which provided clear evidence about incorporation of cationic moieties onto dextrin molecules. In flocculation test, UHP-assisted cationic dextrin revealed higher flocculating activity. Overall results suggested that UHP-assisted cationization reaction could modulate reactivity and flocculating activity of dextrin by controlling pressure levels and reaction mixture compositions, and cationic dextrins likely possessed a higher potential to replace synthetic polymer-based flocculants

Advances in Nutritional Research on Regulatory T-Cells

Many clinical and animal studies have shown that certain dietary components exert anti-inflammatory properties that aid in the amelioration of chronic inflammatory diseases. Among the various proposed channels through which dietary components affect immune responses, regulatory T-cells (Tregs) are emerging as key targets for the dietary prevention of chronic inflammatory diseases. In this review, immunoregulation by Tregs is briefly described, followed by a summary of recent advances and possible applications of techniques for the study of Tregs. In addition, this review provides an overview of the current knowledge on Treg regulation by certain dietary components, including vitamins, omega-3 polyunsaturated fatty acids, and polyphenols. The caveats of previous studies are also discussed in order to highlight the distinctions between dietary studies and immunological approaches. Consequently, this review may help to clarify the means by which nutritional components influence Tregs

Trehalose Inhibits Inflammatory Responses through Mitochondrial Reprogramming in RAW 264.7 Macrophages

Studies reported the beneficial effects of trehalose on metabolic syndromes, hyperlipidemia, and autophagy, but its action mechanisms are still poorly understood. Even though trehalose is digested by disaccharidase and absorbed in the intestine, intact molecules encounter immune cells which form a solid balance between the allowance of nutritive substances and the removal of harmful pathogens. In this regard, the polarization of intestinal macrophages into an anti-inflammatory phenotype through metabolic regulation is emerging as a therapeutic strategy for the prevention of gastrointestinal inflammation. The current study investigated the effects of trehalose on immunological phenotypes, energy metabolism, and LPS-induced macrophage mitochondrial functioning. Results indicate that trehalose reduces prostaglandin E2 and nitric oxide, which are inflammatory mediators of LPS-induced macrophages. In addition, trehalose further significantly suppressed inflammatory cytokines and mediators via energy metabolism reprogramming towards M2-like status in LPS-stimulated macrophages

Rice Bran Oil Attenuates Chronic Inflammation by Inducing M2 Macrophage Switching in High-Fat Diet-Fed Obese Mice

Macrophages are involved in all inflammatory processes from killing pathogens to repairing damaged tissue. In the obese state, macrophages infiltrate into enlarged adipose tissue and polarize into pro-inflammatory M1 macrophages, resulting in chronic low-grade inflammation due to the secretion of inflammatory mediators. Rice bran oil (RBO) is an edible oil containing tocopherols, tocotrienols, and γ-oryzanol. Previous research in normal diet-fed mice suggested that RBO mitigates inflammatory responses by modulating mitochondrial respiration of macrophages. Therefore, we investigated if RBO had an anti-inflammatory effect in diet-induced obese mice by assessing the expression of inflammatory markers in epididymal white adipose tissue (eWAT) and polarization of bone marrow-derived macrophages (BMDMs). Rice bran oil exerted a local anti-inflammatory effect in white adipose tissue by suppressing the production of inflammatory mediators and upregulating transcription of anti-inflammatory genes. Rice bran oil also promoted anti-inflammatory M2 macrophage polarization in BMDMs thereby affecting systemic inflammation. Overall, our in vivo and ex vivo results highlight the potential of RBO as a dietary mediator that can ameliorate obesity-induced chronic low-grade inflammation by mediating the expression of inflammation-related factors and macrophage polarization

Rice Bran Oil Attenuates Chronic Inflammation by Inducing M2 Macrophage Switching in High-Fat Diet-Fed Obese Mice

Macrophages are involved in all inflammatory processes from killing pathogens to repairing damaged tissue. In the obese state, macrophages infiltrate into enlarged adipose tissue and polarize into pro-inflammatory M1 macrophages, resulting in chronic low-grade inflammation due to the secretion of inflammatory mediators. Rice bran oil (RBO) is an edible oil containing tocopherols, tocotrienols, and γ-oryzanol. Previous research in normal diet-fed mice suggested that RBO mitigates inflammatory responses by modulating mitochondrial respiration of macrophages. Therefore, we investigated if RBO had an anti-inflammatory effect in diet-induced obese mice by assessing the expression of inflammatory markers in epididymal white adipose tissue (eWAT) and polarization of bone marrow-derived macrophages (BMDMs). Rice bran oil exerted a local anti-inflammatory effect in white adipose tissue by suppressing the production of inflammatory mediators and upregulating transcription of anti-inflammatory genes. Rice bran oil also promoted anti-inflammatory M2 macrophage polarization in BMDMs thereby affecting systemic inflammation. Overall, our in vivo and ex vivo results highlight the potential of RBO as a dietary mediator that can ameliorate obesity-induced chronic low-grade inflammation by mediating the expression of inflammation-related factors and macrophage polarization

Medium Chain Triglyceride (MCT) Oil Affects the Immunophenotype via Reprogramming of Mitochondrial Respiration in Murine Macrophages

Medium chain triglyceride (MCT) oil has been postulated to modulate inflammatory responses, but the detailed mechanisms have not been fully elucidated. Based on recent studies demonstrating that mitochondrial metabolic reprogramming and immune responses are correlated, the current study sought to determine whether MCT oil controls inflammatory responses through modulation of mitochondria using both in vitro and in vivo models. The mitochondrial metabolic phenotypes of macrophages were assessed according to oxygen consumption rate (OCR). Inflammatory responses were assessed for production of cytokines and expression of activation markers. MCT oil was more rapidly oxidized as observed by increased OCR in macrophages. The production of pro-inflammatory cytokines was down-regulated and anti-inflammatory cytokine was elevated by MCT oil. In addition, classically activated M1 and alternatively activated M2 markers were reciprocally regulated by MCT intervention. Overall, up-regulated &beta;-oxidation by MCT contributes to the anti-inflammatory M2-like status of macrophages, which may aid in the dietary prevention and/or amelioration of inflammation

Effects of Neohesperidin Dihydrochalcone (NHDC) on Oxidative Phosphorylation, Cytokine Production, and Lipid Deposition

The sweetener neohesperidin dihydrochalcone (NHDC) is a precursor for anthocyanins and has been reported to have various bioactivities, including antioxidant and hepatitis inhibitory effects. However, its inflammatory functions and mechanisms of action are poorly understood. In this study, RAW 264.7 murine macrophages were treated with NHDC and its metabolite dihydrocaffeic acid (DHCA), after which cytokine production and mitochondrial respiration were assessed. DHCA significantly down-regulated the secretion of pro-inflammatory cytokines. In contrast, NHDC had a marginal effect, suggesting that the biological metabolism of NHDC to DHCA is required for its anti-inflammatory function. However, both NHDC and DHCA rescued LPS-induced suppression of oxidative phosphorylation, which is a hallmark of anti-inflammatory M2 macrophages. 3T3-L1 adipocytes showed lower fat deposition in the presence of DHCA, while sugar-containing NHDC showed a slight increase in fat deposition. In high-fat diet-induced obese mice, treatment with NHDC successfully down-regulated body weight gain in a dose-dependent manner. Furthermore, M2 polarized bone-marrow-derived macrophages (BMDM) from NHDC-fed mice secreted an increased amount of the anti-inflammatory cytokine IL-10. Overall, these results indicate that NHDC and its physiological metabolite DHCA have the potential to suppress the inflammatory response and obese status

Highly efficient silver nanowire/PEDPT:PSS composite microelectrodes via poly(ethylene glycol) photolithography

Microelectrode technologies have been widely used for a number of applications including optoelectronic and bioelectronics. In this study, we report highly conductive and highly reliable silver nanowire (AgNW)/poly(3,4,-ethylene dioxy thiophene): poly(styrenesulfonate) (PEDOT:PSS) composite microelectrodes fabricated by simple poly(ethylene glycol) photolithography. The electrical properties of AgNW/PEDOT:PSS were examined as functions of the AgNW concentration and layer number, and then compared with those of pure AgNWs. Importantly, the AgNW/PEDOT: PSS composite exhibited a high conductivity with a low sheet resistance of 1.22 Omega/rectangle as well as an excellent electrical standard deviation of 0.96 Omega/rectangle in a reliability test. We also demonstrated that these composite micropatterns were completely transferred from the glass to a flexible hydrogel by a direct transfer process. Moreover, the composite microelectrodes exhibited increases in the electrical resistance of only 11 and 24% after over 300 and 500 bending cycles, which were 65 and 90% enhancements compared to the single AgNW microelectrode, respectively. This novel approach could become a low-cost and efficient design for fabricating high-performance microelectrodes