Immunopotentiation of NKT cells by low-protein diet and the suppressive effect on tumor metastasis.
Mice were fed with a 5% low-protein diet for two weeks, at which point tumor inoculation was conducted. Following this inoculation, the 5% low-protein diet was continued. On the other hand, control mice were fed with a normal diet (25% protein) and such diet was continued after tumor inoculation. In comparison with control mice, mice fed with the 5% low-protein diet showed a prominent prolongation of survival rate when injected with both EL4 and 3LL tumors. Interestingly, CD1d(-/-) mice, which primarily lack natural killer T (NKT) cells, did not show the prolongation of survival rate even when they received a 5% low-protein diet. The most striking phenomenon seen in tumor-bearing mice fed with the 5% low-protein diet was the suppression of tumor metastasis to the liver and lung. Such suppression was not seen in CD1d(-/-) mice who were fed with a 5% low-protein diet. Phenotypic study revealed that the proportion of NKT cells after tumor inoculation decreased in the mice fed with a normal diet. However, such decrease did not occur in mice fed with the 5% low-protein diet. Reflecting the activation of NKT cells by feeding, tumor cytotoxicity and cytokine production were also augmented by the 5% low-protein diet. These results suggest that a low-protein diet has the potential to augment the innate immunity against tumors, especially mediated by the activation of NKT cells.
Li
Changchun
C
Department of Immunology, Niigata University School of Medicine, Niigata 951-8510, Japan.
Bai
Xuefeng
X
Wang
Sen
S
Tomiyama-Miyaji
Chikako
C
Nagura
Toru
T
Kawamura
Toshihiko
T
Abo
Toru
T
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism; D055610:Antigens, CD1d; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018753:Diet, Protein-Restricted; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008113:Liver Neoplasms / Q000178:diet therapy / Q000556:secondary*; D008175:Lung Neoplasms / Q000178:diet therapy / Q000556:secondary*; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis / Q000628:therapy; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D018949:Antigens, CD1; D055610:Antigens, CD1d; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma