Effects of exercise training and supplementation with selenium nanoparticle on T-helper 1 and 2 and cytokine levels in tumor tissue of mice bearing the 4 T1 mammary carcinoma.

OBJECTIVES: Physical exercise decreases the incidence of breast cancer and also improves survival in breast cancer patients. However, the mechanistic basis of these protective effects of exercise is not well known. Changes in tumor cytokines, such as oncostatin-M (OSM), have been associated with modulation of antitumor immune responses in breast cancer. Exercise and antioxidants such as selenium affect both antitumor immune responses as well as tumor cytokine expression. Thus, the aim of this study was to determine the effects of aerobic exercise training (AET) and selenium nanoparticle (SeNP) administration on T-helper 1 and 2 and tumor tissue cytokines in mice bearing the 4 T1 mammary carcinoma. METHODS: We examined the effects of 6 wk of AET and SeNP administration (100 µg three times/wk) on tumor size, concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-4 and OSM in tumor tissue and INF-γ and IL-4 in splenocytes of 64 mice bearing the 4 T1 mammary carcinoma. RESULTS: AET increased OSM levels in tumor tissue. Moreover, AET increased levels of TNF-α in tumor tissue, whereas SeNP supplementation decreased IL-4 levels tumor tissue. Also, the combination of AET and SeNP administration decreased tumor volume and increased T-helper 1 cytokines in the splenocytes of tumor-bearing mice. CONCLUSION: These findings suggest that the combination of AET and SeNP supplementation effects antitumor immune responses in splenocytes, whereas AET induced antitumor cytokines, such as OSM and TNF-α in tumor tissue.

Mesenchymal stem cells alter macrophage immune responses to Leishmania major infection in both susceptible and resistance mice.

Mesenchymal stem cells (MSCs) are attracted to inflammation site and switch immune system to modulate inflammatory responses. This ability makes MSCs the best candidate cells for stem cell therapy of infection diseases. Therefore, we aimed to evaluate the modulatory effect of adipose-derived MSCs (AD-MSCs) on macrophages in Leishmania (L.) major infection. Macrophages and MSCs were isolated from both susceptible (BALB/c) and resistance (C57BL/6) strains. After co-culture of AD-MSCs with macrophages using a transwell system, we assessed MSCs-educated macrophage responses to L. major infection. Our results indicated suppression in levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) of MSCs co-cultured macrophages in response to L. major infection. To clarify the effects of this suppression on inflammatory conditions, TNF-α/IL-10 ratio was calculated, indicating an increase in TNF-α/IL-10 ratio in MSCs co-cultured groups. The higher TNF-α/IL-10 ratio was observed in BALB/c macrophages co-cultured with BALB/c MSCs. Nitric oxide (NO) assay presented a significant reduction in the supernatant of all MSCs co-cultured groups compared to control. We observed a significant reduction in phagocytosis of MSCs co-cultured groups in response to L. major infection without any significant differences in the phagocytic index. In conclusion, our results represented a new spectrum of immunomodulation induced by MSCs co-cultured with macrophages in response to L. major infection. The magnitude of immunoregulation was different between BALB/c and C57BL/6 strains. Our findings also showed that MSCs exerted potential effect of M1 polarization due to unequal decrease in levels of TNF-α and IL-10 when we considered TNF-α and IL-10as representatives of M1 and M2 phenotypes, respectively. Induction of inflammatory cytokine milieu and reduction in level of IL-10 provides a new hope for stem cell therapy of leishmaniasis in susceptible models.