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Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.

Dang VT, Tanabe K, Tanaka Y, Tokumoto N, Misumi T, Saeki Y, Fujikuni N, Ohdan H - PLoS ONE (2014)

Bottom Line: Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting.Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05).These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

ABSTRACT
Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)+ and CD69+ natural killer cells were significantly elevated (n = 7, p <0.01), as determined by flow cytometric analysis. Furthermore, we found that TRAIL- natural killer cells that were adoptively transferred into Rag-2-/- γ chain-/- mice could convert into TRAIL+ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05) in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05). In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05). These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

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Distribution of TRAIL and CD69 expression in liver natural killer cells in response to starvation.Liver lymphocytes from fed mice and 3-day-fasted mice were stained with monoclonal antibodies and counted using flow cytometry. Numbers of (A) TCRβ− NK1.1+ natural killer (NK) cells, (B) TRAIL+/− NK cells, and (C) CD69+/− NK cells per gram of liver tissue are presented in bar graphs as mean plus standard deviation (n = 7); *p <0.05 as analyzed by the independent samples T test.
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pone-0110748-g002: Distribution of TRAIL and CD69 expression in liver natural killer cells in response to starvation.Liver lymphocytes from fed mice and 3-day-fasted mice were stained with monoclonal antibodies and counted using flow cytometry. Numbers of (A) TCRβ− NK1.1+ natural killer (NK) cells, (B) TRAIL+/− NK cells, and (C) CD69+/− NK cells per gram of liver tissue are presented in bar graphs as mean plus standard deviation (n = 7); *p <0.05 as analyzed by the independent samples T test.

Mentions: The influence of fasting on the absolute number of NK cells was also examined. The total number of liver resident NK cells in a unit weight of liver tissue did not differ between fasted and fed mice, indicating that, under fasting conditions, the number of TRAIL− NK cells decreased, while that of TRAIL+ NK cells increased (Figure 2A, B).


Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.

Dang VT, Tanabe K, Tanaka Y, Tokumoto N, Misumi T, Saeki Y, Fujikuni N, Ohdan H - PLoS ONE (2014)

Distribution of TRAIL and CD69 expression in liver natural killer cells in response to starvation.Liver lymphocytes from fed mice and 3-day-fasted mice were stained with monoclonal antibodies and counted using flow cytometry. Numbers of (A) TCRβ− NK1.1+ natural killer (NK) cells, (B) TRAIL+/− NK cells, and (C) CD69+/− NK cells per gram of liver tissue are presented in bar graphs as mean plus standard deviation (n = 7); *p <0.05 as analyzed by the independent samples T test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214715&req=5

pone-0110748-g002: Distribution of TRAIL and CD69 expression in liver natural killer cells in response to starvation.Liver lymphocytes from fed mice and 3-day-fasted mice were stained with monoclonal antibodies and counted using flow cytometry. Numbers of (A) TCRβ− NK1.1+ natural killer (NK) cells, (B) TRAIL+/− NK cells, and (C) CD69+/− NK cells per gram of liver tissue are presented in bar graphs as mean plus standard deviation (n = 7); *p <0.05 as analyzed by the independent samples T test.
Mentions: The influence of fasting on the absolute number of NK cells was also examined. The total number of liver resident NK cells in a unit weight of liver tissue did not differ between fasted and fed mice, indicating that, under fasting conditions, the number of TRAIL− NK cells decreased, while that of TRAIL+ NK cells increased (Figure 2A, B).

Bottom Line: Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting.Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05).These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

ABSTRACT
Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)+ and CD69+ natural killer cells were significantly elevated (n = 7, p <0.01), as determined by flow cytometric analysis. Furthermore, we found that TRAIL- natural killer cells that were adoptively transferred into Rag-2-/- γ chain-/- mice could convert into TRAIL+ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05) in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05). In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05). These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

Show MeSH
Related in: MedlinePlus