The effects of bone marrow-derived mesenchymal stem cells on ovalbumin-induced allergic asthma and cytokine responses in mice.

OBJECTIVES: Allergic Asthma is an inflammatory disease of the lungs that is characterized by increased infiltration of leukocytes into the airways, limiting the respiratory function. Studies suggest that a defective general regulatory system against inflammation could be a significant factor in allergic asthma. It has been shown that Mesenchymal stem cells (MSCs) have a cellular immunosuppressive therapeutic potential for inflammatory disorders. We investigated whether administration of MSCs during allergen challenge would affect the underlying mechanisms in allergic airways inflammation. MATERIALS AND METHODS: Fifty mice were used in five control and experimental groups; the experimental mice sensitized by intraperitoneal injection of OVA and aluminum hydroxide emulsion on days 0, 7, and 14, were then challenged intranasally with OVA or sterile PBS on days 14, 25, 26, and 27. Before allergen challenge on day 14, experimental mice received tail vein injection of MSCs in PBS, whereas control mice received PBS alone. Cytokine and IgE analyses were carried out using lung washes as well as serum samples. RESULTS: Our, results showed that MSCs significantly reduced total cells and eosinophilia and serum OVA-specific IgE concentration in OVA-sensitized and challenged mice. Also, results showed that MSCs markedly inhibited expressions of Th2 and Th17 cytokines and elevated levels of Treg cytokines. CONCLUSION: we found that administration of MSCs could be used as a potential therapeutic approach for allergic asthma.

Treatment of undifferentiated colorectal cancer cells with fish-oil derived docosahexaenoic acid triggers caspase-3 activation and apoptosis.

BACKGROUND: The effectiveness of chemotherapy is often limited by the side effects on normal tissues. Consequently, the search for new therapeutic agents with minimal toxicity is of particular interest in cancer management. Many studies have shown that docosahexaenoic acid (DHA) have cytotoxic effects against different kinds of cancer cells. However, little attention has been paid to explore the effect of DHA on undifferentiated colorectal cancer cells. In this study, the effects of DHA on LS174T cells as an early stage of tumor initiation were investigated. MATERIALS AND METHODS: Tumor cells were treated to various concentrations of DHA and proliferation, survivin expression, caspase-3 activation, and apoptosis were evaluated by different cellular and molecular techniques. RESULTS: Following 48 h treatment, proliferation was measured to be 73 ± 4.5% (P = 0.000), 53 ± 5.7% (P = 0.000) and 26.3 ± 3.5% (P = 0.000) for 50, 100, and 150 µM DHA, respectively compared to untreated cells. This molecule induced 63% (P = 0.001) and 46% (P = 0.000) decrease in survivin messenger ribonucleic acid (mRNA) level as well as 1.8 (P = 0.001) and three-fold (P = 0.000) increase in caspase-3 activation for 50 and 100 µM DHA, respectively compared to untreated cells. Our evidence showed that survivin mRNA is expressed at the early stage of colorectal cancer cells and DHA-treated cells expressed markedly a lower survivin mRNA compared to untreated cells. CONCLUSIONS: DHA is an attractive repressor of survivin expression, increases caspase-3 and apoptosis in colorectal cancer cells and may provide a novel approach to the treatment of colorectal cancer at the early stage of tumor initiation.

Treatment of LS174T colorectal cancer stem-like cells with n-3 PUFAs induces growth suppression through inhibition of survivin expression and induction of caspase-3 activation.

PURPOSE: Colorectal cancer stem cells (CCSCs) are thought to contribute to tumor initiation, progression, metastasis, chemo-resistance and therapy failure. Therefore, assessment of the effectiveness of agents with anti-proliferative activities against CCSCs is warranted. Several studies have shown that different tumorigenic steps, ranging from initiation to metastasis, can be affected by n-3 polyunsaturated fatty acids (PUFAs). Here, we evaluated the effects of the PUFA components docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), alone or in combination, on LS174T cells that serve as a model for colorectal cancer initiating cells with stem cell-like properties. METHODS: LS174T cells were treated with 50, 100 and 150 µM DHA and EPA, or equal mixtures of DHA/EPA (i.e., 25/25, 50/50 and 75/75 µM), after which cell number, viability, growth inhibition, survivin expression, caspase-3 activation and apoptotic rate were evaluated. RESULTS: We found that treatment of LS174T cells with increasing PUFA concentrations significantly increased growth inhibition in a dose- and time-dependent manner. After a 72 h treatment with 150 µM DHA and EPA, or their combination (75/75 µM), growth rates were inhibited by 80.3 ± 5.5%, 79.3 ± 5% and 71.1 ± 1%, respectively, compared to untreated cells. We also found that treatment for 48 h with 100 µM DHA and EPA, or their combination (50/50 µM), resulted in 2.9-, 3- and 2.6-fold increases in caspase-3 activation, as well as 54, 62.4 and 100% decreases in survivin mRNA expression levels, respectively, compared to untreated cells. Low survivin mRNA levels combined with high caspase-3 activity levels were found to correlate with a higher growth inhibition in PUFA-treated cells. DHA appears to be a more potent growth inhibitor than EPA and the DHA/EPA combination. An increase in the number of apoptotic cells (early + late), ranging from 12.9 to 44.7%, was observed with increasing DHA doses. CONCLUSION: From our data we conclude that PUFAs induce growth inhibition via targeting survivin expression in LS174T cells, which serve as a model for CCSCs.

Effect of carotenoid ß-cryptoxanthin on cellular and humoral immune response in rabbit.

Beta-cryptoxanthin (b-Cr) is a pro-vitamin A and one of the major carotenoids that can be commonly found in mammalian serum and tissues. Foods rich in certain fatty acids are known to be effective to gain a healthy immune system. In the present study, we evaluated the effect of b-Cr on rabbit humoral and cellular immune responses to have a better vision about the mechanism of effect of carotenoids on immune system. Twenty rabbits were randomly divided into five groups (4 per group): Groups consisted of: 1) control group (normal saline; 2) b-Cr (control); 3) vaccine control; 4) 5 mg/kg b-Cr o.p. + vaccine; 5) 10 mg/kg b-Cr o.p. + vaccine. Blood samples were obtained from the marginal ear artery at three time points: days 0, 14 and 21 of the study. Blood CD4+ and CD8+ lymphocytes and Serum Immunoglobulin and Cytokines content were evaluated. Results show that b-Cr administration increased the blood CD4+ lymphocytes count (P > 0.01). Serum IgG, IgM and IgA levels increased (P > 0.05) following b-Cr administration. b-Cr treatment increased serum IL-4 levels (P > 0.05). According to presented results, b-Cr may increase the humoral immunity in mammals. So, it would possible has a potentially beneficial effect on health and on prevention of the immunity related diseases.