Biomedical subjects

Kenichi Matsunaga

Publications and source records attributed to Kenichi Matsunaga.

8 recordsLinked to original sources

PubMed2006

Protective effect of a protein-bound polysaccharide, PSK, on CLP-induced sepsis in mice transplanted orthotopically with colon tumor.

We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against sepsis induced by cecal ligation and puncture (CLP). (a) In BALB/c mice that had received intracecal transplantation of colon 26 (C26) tumor, CLP with a 21-gauge needle significantly shortened the survival time, compared with that of non-tumor-bearing mice. Oral administration of PSK to such mice resulted in a significant prolongation of the survival time and increase of the survival rates. The effects were dependent on the timing of PSK administration and the dose. (b) CLP significantly increased the IL-10 level in serum, the IL-10 gene expression by spleen cells, the number of IL-10-producing CD4-positive T cells, and the productivity of IL-10 by spleen of tumor-bearing mice compared with that of non-tumor-bearing mice. PSK administration to such mice suppressed the increase. Further, PSK prevented the reduction of gene expression of IFN-gamma and the number of IFN-gamma-producing CD4-positive T cells and IFN-gamma productivity by spleen cells of tumor-bearing CLP-treated mice. (c) Treatment with anti-IFN-gamma monoclonal antibody before CLP significantly reduced the effects of PSK. These findings suggest that the protective effect of PSK on the CLP-induced sepsis in mice transplanted orthotopically with C26 tumor is possibly mediated by suppression of IL-10 and promotion of IFN-gamma.

Animals↗

PubMed2005

Isolation and characterization of a novel immunomodulatory alpha-glucan-protein complex from the mycelium of Tricholoma matsutake in basidiomycetes.

Tricholoma matsutake, a high-class edible mushroom in Japan, has been reported to have excellent biological activities, but difficulty in cultivating the fruit bodies and limited bulk availability have restricted detailed studies. We have developed a method of culturing in tanks, enabling the bulk supply of the mycelia. The preparation (CM6271) exerts modulative effects on the immune competence of mice and rats. In this study, a sodium hydroxide extract of CM6271 was defatted followed by fractionation with a combination of ion exchange chromatography and gel filtration in order to identify the components involved in the expression of the activity, and a single peak fraction (MPG-1) was obtained with reversed phase chromatography. MPG-1 was a glycoprotein (sugar:protein ratio, 94.3:5.7) with a relative molecular mass of 360 kDa, and the sugar moiety contained about 90% glucose. NMR spectra and methylation analysis revealed that the alpha-1,4-linkage was the predominant glucan linkage with alpha-1,6- and alpha-1,2-linkages in the minority. The amino acid composition in the protein moiety was rich in glutamine, alanine, asparagine, leucine, glycine, valine, serine, threonine, isoleucine, and proline. MPG-1 was resistant to degradation with amylase or protease. The oral administration of MPG-1 promoted, in a dose-dependent manner, the recovery of the mouse natural killer cell activity and serum IL-12 level that had been reduced by the loading of restraint stress. The dose of MPG-1 (25 mg/kg) required for the expression of the effect decreases to 1/12 of that of CM6271 (300 mg/kg). Furthermore, MPG-1 formed a complex with TGF-beta1 in vitro, modulating the biological activity of TGF-beta1 by binding to its active form. These results indicate that the mycelium of T. matsutake contains a novel alpha-glucan-protein complex with immunomodulatory activities.

Animals↗

PubMed2004

Inhibition of decrease in natural killer cell activity in repeatedly restraint-stressed mice by a biological response modifier derived from cultured mycelia of the basidiomycete Tricholoma matsutake.

OBJECTIVE: To develop a method to cope with stress-induced reduction in immunocompetence, we evaluated the immunomodulatory activities of a biological response modifier derived from the mycelia of the basidiomycete Tricholoma matsutake (CM6271) in mice under repeated restraint stress. METHODS: C57BL/6 mice were inserted, one per tube, into 50-ml polypropylene tubes into which more than 30 ventilation holes had been drilled, and were restrained everyday for 20 days in this fashion for set periods of time. Natural killer (NK) cell activity and NK1.1-positive cell counts in the spleen, ACTH and corticosterone levels in the blood were determined. CM6271 was orally administered daily during the restraint stress period. RESULTS: (1) When the mice were restrained in a confined space for 6 h per day for 20 days, the NK cell activity and the NK1.1-positive cell counts in the spleen significantly decreased after day 5 with an increase in the blood ACTH and corticosterone levels. (2) Oral administration of CM6271 during the restraint stress period significantly prevented the stress-induced decrease in NK cell activity. The effect was dependent on the timing, duration, and doses administered. (3) CM6271 did not significantly affect the splenic NK1.1-positive cell counts or the levels of blood ACTH and corticosterone in restraint-stressed mice. CONCLUSION: The above findings suggest that CM6271 inhibits the restraint stress-induced decrease of NK cell activity in a timing of administration and dose-dependent manner.

Animals↗

PubMed2003

Expression of matrix metalloproteinase, tissue inhibitors of metalloproteinase and adhesion molecules in silicotic mice with lung tumor metastasis.

The number of metastatic foci in silicotic mice is approximately 1.5-fold that in normal mice and in mice treated with TiO2 as inert particles. Expression of matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) and selectins was investigated in silicotic mice with lung tumor metastasis. Expression of MMP-9 and P-selectin mRNA, but not MMP-2 and E-selectin, increased significantly, showing decreases of the ratio of expression in TIMPs/MMP-9 in tumor-bearing silicotic mice compared with the tumor-bearing normal mice and mice treated with TiO2. Pretreatment with anti-P-selectin antibody inhibited number of metastatic foci significantly in silicotic mice, while pretreatment of animals with anti MMP-9 antibody showed slight decrease of metastatic foci. This evidence indicated that up-regulation of P-selectin expression contributed to enhanced rate of tumor metastasis in lung with silicosis.

Animals↗

PubMed2003

Enhanced recovery of NK cell activity in mice under restraint stress by the administration of a biological response modifier derived from the mycelia of the basidiomycete Tricholoma matsutake.

Some types of stressor act on the immune system via the network comprising the endocrine-immune-nervous systems, and are reportedly responsible for the onset of diseases as well as giving impetus to their advance. It is important for the maintenance and promotion of health to cope with stress-induced changes in immunocompetence. Therefore, we studied the effects of administration of a novel biological response modifier (CM6271) derived from the mycelia of the basidiomycete Tricholoma matsutake on the NK cell activity in mice under restraint stress, in order to evaluate its potential to modulate immune responsiveness in stress-loaded individuals. (1) When C57BL/6 mice were restrained in 50-ml tubes for more than 6 h, splenic NK cell activity decreased significantly, but recovered gradually after the mice were released. The extent of the reduction of activity and the degree of recovery depended on the duration of the restraint. (2) The oral administration of CM6271 caused a significant acceleration of the recovery of the activity. This effect was dependent on the timing of administration and the dose given. (3) The administration of CM6271 had no clear effect on the blood levels of ACTH, corticosterone or lipid peroxide levels in the liver. These findings suggest that CM6271 promotes recovery from the decrease in NK cell activity induced by restraint stress.

Adrenocorticotropic Hormone↗

PubMed2003

Protective effects of a protein-bound polysaccharide, PSK, against Candida albicans infection in syngeneic tumor-bearing mice via Th1 cell functions.

We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against Candida albicans infection. In BALB/c mice that had received subcutaneous (sc) transplantation of fibrosarcoma Meth A, viable fungal counts were increased in the kidney and the mean survival period was shortened after challenge with C. albicans, compared with healthy mice. Oral administration of PSK to such mice resulted in a significant decrease of viable fungal counts and a prolongation of the mean survival period. The ratio of CD4-positive T cells in the spleen was decreased in noninfected tumor-bearing mice and the decrease was prevented by PSK, although in vitro anticandida activities of phagocytes were not significantly affected by tumor burden or PSK. Further, intracellular interferon (IFN)-gamma productivity was enhanced and the number of IFN-gamma-producing CD4-positive T cells was enhanced by PSK. PSK enhanced the gene expression of interleukin (IL)-12 and IFN-gamma in the spleen of tumor-bearing mice inoculated with C. albicans. Treatments with anti-IL-12 or anti-IFN-gamma antibody reduced the anti-infectious effects of PSK. These findings suggest that the protective effect of PSK on sublethal inoculation with C. albicans in tumor-bearing mice is possibly mediated by Th1 cell functions.

Animals↗

PubMed2003

[Effect of PSK on Th1/Th2 balance in tumor-bearing mice].

We investigated the effect of PSK on Th1/Th2 balance in tumor-bearing mice. PSK was intraperitoneally administered to Meth A-bearing BALB/c mice, and PSK caused regression of the Meth A tumor. The results of Winn assay suggested that the effect of PSK was dependent on CD4+T cells. Furthermore, spleen cells were cultured with mitomycin C-treated Meth A, after which the cytokine concentration was measured by ELISA. IFN-gamma production was increased and IL-4 showed almost no change in PSK-administered mice. In another experiment, PSK was orally administered to colon 26-bearing mice in which tumors were inoculated into the subserosal space of the cecum. Mesenteric lymph nodes cells were cultured with mitomycin C-treated colon 26 cells. IFN-gamma production was increased, but not so much as to be statistically significant, and IL-4 was significantly decreased in PSK-administered mice. PSK increased IFN-gamma and IL-12 p70 production and decreased IL-4 production when spleen cells were stimulated with Con A together with PSK in vitro. As suggested from these results, PSK might induce cytokine production that works for Th1 differentiation, and suppress cytokine production that works for Th2 differentiation, and shift the Th1/Th2 balance toward Th1 dominance in tumor-bearing mice.

Animals↗

PubMed2002

Expression and mutation of p53 gene in the lung of mice intratracheal injected with crystalline silica.

The genotoxic effect of crystalline silica (Qt) in the lung was studied to clarify that silicosis conferred a significant increase in risk subsequent lung cancer. C57BL/6N mice received a single tracheal injection of Qt at dose of 2 mg/mouse. Lung p53mRNA was suppressed significantly, but no change of p21mRNA 15 months after treatment. Mutation of p53 gene was not identified at 15 months in the Qt group. Silicotic lesions were observed in the lungs of Qt group, but silicosis with pulmonary neoplasia was no detected. These results indicated that genetic changes in the silicotic lung might lead to facilitation of carcinogenesis.

Animals↗