Keita Kudoh

Effects of dietary docosahexaenoic acid on surface molecules involved in T cell proliferation.

It is known that n-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) suppress immunity as compared with n-6 PUFA such as linoleic acid (LA), but the mechanism involved in this phenomenon is still unclear. The present study was designed to assess the effect of dietary DHA on the surface molecules involved in T cell proliferation. Weanling male C57BL/6 mice were divided into four dietary groups that were fed a 10% fat diet for 4 weeks varying in amounts of DHA and LA. As the dietary DHA concentration increased, the surface expression of CD4 and CD8 on splenic T cells decreased, while that of CD28 increased. The surface expression of CD3, however, was invariable in all dietary groups. DNA synthesis of splenic T cells, induced by CD3 crosslinkage with anti-CD3 epsilon monoclonal antibody in the presence of CD28-mediated costimulation, increased as the DHA concentration was elevated. These observations suggest that diets rich in DHA exert some of their immunomodulatory effects by a downregulation of surface expression of CD4 and CD8 and by an upregulation of CD28-mediated costimulatory signal.

Dietary n–3 Polyunsaturated Fatty Acid and Status of Immunocompetent Cells Involved in Innate Immunity in Female Rats

The aim of this study was to estimate the contributions of dietary n–3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n–6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n–3 PUFA (n–3 diet) and the other an n–6 PUFA (n–6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor α in the rats fed the n–3 diet, compared with rats fed the n–6 diet. NK cell activity was reduced by consumption of the n–3 diet. This study suggests that consumption of n–3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.

Effects of isothiocyanates on growth and metastaticity of B16‐F10 melanoma cells

3-Methylthiopropyl (MTPITC) and 5-methylthiopentyl isothiocyanate (MTPeITC), natural compounds found in human diets, were assayed for an inhibitory activity against the growth of B16-F10 murine melanoma cells in culture. MTPITC and MTPeITC showed a potent cytostatic effect; the two agents exhibited median inhibitory concentrations of 48 and 170 nM, respectively. Oral administration of 10 mumol MTPeITC on Day 1 after intravenous tumor cell injection achieved a marked reduction of pulmonary colonization in syngeneic mice. However, it caused atrophy of the thymus and selective loss of CD4+CD8+ cells in thymocytes. On the other hand, treatment with MTPITC showed no influence on pulmonary metastaticity or thymocytes. Neither MTPITC nor MTPeITC caused significant changes in the responsiveness of the splenocytes and thymocytes to mitogen. These results suggest that MTPeITC can protect against metastaticity as well as cell growth of tumor cells, regardless of the disadvantageous action on the thymus.

Dietary fiber and gastrointestinal functions

Publisher Summary This chapter deals with the gastrointestinal functions of several dietary fibers with hydrophilic and hydrophobic properties and describes a series of experiments. In the first experiment, male rats of the Sprague-Dawley strain are fed diets containing cellulose powder, curdlan, and gellan gum at 5% for 4 weeks. Compared with the curdlan group, shortened gastrointestinal transit time, increased weight of the cecal contents, and feces are observed in the gellan gum group. The amounts of short-chain fatty acids and lactic acid in the cecum are markedly increased in the curdlan group. The hepatic cholesterol concentration in the curdlan group is significantly decreased compared with that in the cellulose and gellan gum groups. These results reveal that curdlan is easily hydrolyzed and fermented by intestinal bacteria but not so easily in the gellan gum. The reduction of hepatic cholesterol concentration in the curdlan group may be attributed to a remarkable increase in fermentation products by the intestinal bacteria. In the subsequent experiments, rats are given diets containing cellulose, arable gum, corn husk (Celfur), glucomannan, curdlan, and indigestible dextrin at 5% for 3 weeks. Some kinds of dietary fiber induce proportions of κ-light chain and IgA-presenting B lymphocytes in the mucosa of small intestine and cecum, and increase IgA secretion to cecal contents and feces, but the degree of responses differs depending upon the type of dietary fiber. These results show that some dietary fibers are possibly there in the intestinal immune system of rats, suggesting a new development on physiological functions of dietary fiber.

Dietary curdlan suppresses dimethylhydrazine-induced aberrant crypt foci formation in Sprague-Dawley rat

The effect of curdlan (CD), a β-1,3-glucan produced by Alcaligenes faecalis var. myxogenes, on 1,2-dimethylhydrazine (DMH) induced aberrant crypt foci (ACF) formation in colon was studied in male Sprague-Dawley rats. All rats were received subcutaneous injection of DMH (12 mg/kg body weight) once a week for two weeks. At one week after last DMH injection, rats were fed experimental diets containing an each 5% of cellulose powder (CP), CD and gellan gum for 32 days. The total number of ACF formed in colon and cecal beta-glucronidase activity in the CD-fed group were significantly reduced to 53% and 57% as compared with those in the CP-fed group, respectively. The concentration of butyrate and beta-glucosidase activity were significantly increased in cecal contents of the CD-fed group. The concentrations of cecal p-cresol and phenol in the CD-fed group were significantly decreased as compared with those in the CP-fed group. The present study demonstrated that the administration of CD suppresses DMH-induced ACF formation in rats.

Effects of a Partially Hydrolyzed Curdlan on Serum and Hepatic Cholesterol Concentration, and Cecal Fermentation in Rats

A significant reduction was observed for serum and hepatic cholesterol concentrations in the rats fed diet containing a 5% partially hydrolyzed curdlan (PHCD), whereas only the hepatic cholesterol concentration was decreased in the curdlan (CD)-fed rats. The cecal contents in the CD group contained a significantly larger amount of short-chain fatty acids, but not those in the PHCD group. CD, but not PHCD, significantly increased the population of cecal bifidobacteria. From the in vitro fermentation test with cecal contents from cellulose powder (CP) and CD-fed rats, PHCD proved to be easily fermented by both cecal contents; incidentally CD was more susceptible to the cecal contents from CD-fed rats than to those from CP-fed rats. These results suggest that PHCD is involved in the modulation of lipid metabolism and intestinal microflora through a different manner from the native CD in rats.