FSH regulates RA signaling to commit spermatogonia into differentiation pathway and meiosis.

BACKGROUND: Spermatogenesis is a complex process that is controlled by interactions between germ cells and somatic cells. The commitment of undifferentiated spermatogonia to differentiating spermatogonia and normal spermatogenesis requires the action of gonadotropins. Additionally, numerous studies revealed the role of retinoic acid signaling in induction of germ cell differentiation and meiosis entry. MAIN TEXT: Recent studies have shown that expression of several RA signaling molecules including Rdh10, Aldh1a2, Crabp1/2 are influenced by changes in gonadotropin levels. Components of signaling pathways that are regulated by FSH signaling such as GDNF, Sohlh1/2, c-Kit, DMRT, BMP4 and NRGs along with transcription factors that are important for proliferation and differentiation of spermatogonia are also affected by retinoic acid signaling. CONCLUSION: According to all studies that demonstrate the interface between FSH and RA signaling, we suggest that RA may trigger spermatogonia differentiation and initiation of meiosis through regulation by FSH signaling in testis. Therefore, to the best of our knowledge, this is the first time that the correlation between FSH and RA signaling in spermatogenesis is highlighted.

Oral administration of Lactobacillus acidophilus induces IL-12 production in spleen cell culture of BALB/c mice bearing transplanted breast tumour.

Lactic acid bacteria can affect the maturation of immune cells and their products not only in the gut but also on the systemic immune organs such as lymph nodes and spleen. In the present work, we studied the effects of oral administration of Lactobacillus acidophilus on the immune responses of BALB/c mice bearing transplanted breast tumour. Two groups of female inbred BALB/c mice, each containing nine mice as test and control, were used. The L. acidophilus ATCC4356 strain was inoculated in DeMan-Rogosa-Sharpe broth and cultivated for 24 h at 37 degrees C. Then, it was collected by centrifugation, and was washed and suspended in PBS. Afterwards, 0.5 ml/d of this suspension, which contained 2.7 x 108 colony forming units/ml of bacteria, was orally administered to the mice by gavage, 14 d before tumour transplantation and 30 d after that with 3-d intervals. Similar to the test mice, the control mice received an equal volume of PBS. The results showed that oral administration of L. acidophilus increased the production of IL-12 (P < 0.05) and decreased the level of transforming growth factor beta (P = 0.05) in the splenocyte culture. Moreover, the growth rate of tumour in the test mice decreased (P < 0.01), and the results of delayed-type hypersensitivity assay after 48 h were risen (P < 0.05) in comparison with the controls. Results suggest that daily consumption of L. acidophilus can improve the production of immunomodulatory cytokine IL-12 in the splenocyte culture, which was stimulated by tumour antigen in BALB/c mice bearing transplanted breast tumour. But further studies are needed to find out some other possible mechanisms of this effect.

Heat shock proteins enriched-promastigotes of Leishmania major inducing Th2 immune response in BALB/c mice.

BACKGROUND: Heat shock proteins (HSP) are highly conserved molecules with many immunological functions. They are highly immunogenic with important role in cancer immunotherapy and in vaccine development against infectious diseases. As adjuvant, HSP can augment the immunogenicity of weak antigens and can stimulate antigen presenting cells. Although vaccines have been successful for many infectious diseases, progress in leishmaniasis has not been achieved. In this report, the protective effect of HSP-enriched soluble leishmania antigen (SLA) was determined. METHODS: BALB/c mice were immunized 3× with HSP-enriched SLA and SLA alone and 10 days after final boost. They were infected with 106 stationary phase promastigote of Leishmania major and immunological responses were followed until nine weeks. RESULTS: No significant differences were observed in lymphocyte proliferation, footpad swelling, parasite burden, nitric oxide or IL-12 cytokine between HSP-enriched or SLA groups. Although the levels of IFN-γ, IL-4, TGF-ß, IgG1 and IgG2b were increased in both groups, IFN-γ was significantly higher in SLA group and IgG2a in HSP-enriched SLA. CONCLUSION: These results indicate that HSP direct the immune system towards Th2 pattern and does not have protective role in L. major infection.

Lactobacillus casei ssp.casei induced Th1 cytokine profile and natural killer cells activity in invasive ductal carcinoma bearing mice.

Lactic acid bacteria which are used as probiotics have ability to modulate immune responses and modify immune mechanisms. It has also been indicated that some strains of this family can affect the immune responses against solid tumors. In the present work, we proposed to study the effects of oral administration of L.cacesi ssp casei on the NK cells cytotoxicity and also production of cytokines in spleen cells culture of BALB/c mice bearing invasive ductal carcinoma. 30 female In-bred BALB/c mice, were used and divided in two groups of test and control each containing 15 mice. Every day from 2 weeks before tumor transplantation 0.5 ml of PBS containing 2.7×108 CFU/ml of L.casei spp casei was orally administered to the test mice and it was followed 3 weeks after transplantation as well with 3 days interval between each week. Control mice received an equal volume of PBS in a same manner. Results showed that oral administration of L. casei significantly increased the production of IL-12 and IFN-γ (P<0.05) and increased the natural killer cells (NK) cytotoxicity in spleen cells culture of test mice (P<0.05). It has also been demonstrated that the growth rate of tumor in the test mice was decreased and their survival was significantly prolonged in comparison to the controls. Our findings suggest that daily intake of L.casei can improve immune responses in mice bearing invasive ductal carcinoma, but further studies are needed to investigate the other involving mechanisms in this case.

Candida albicans structural and secreted proteins modulate CD4/CD8 ratio in tumor infiltrating lymphocytes of spontaneous adenocarcinoma bearing mice.

BACKGROUND: Candida albicans is one of the most important opportunistic pathogens that suppress immunologic mechanisms of the host. It is speculated that structural and secretory proteins of C. albicans have immunomodulatory effects in cancer. OBJECTIVE: To evaluate the effects of C. albicans structural and secreted proteins on intratumoral CD4/CD8 ratio as well as the survival rate in BALB/c tumor model. METHODS: Structural and secretory proteins from C. albicans were isolated and examined for their effects on tumor growth and survival of adenocarcinoma bearing mice. RESULTS: The results indicated that in mice treated with C. albicans structural protein, the survival rate significantly decreased compared with the control groups. Also, mice treated with secretory proteins showed a decrease in survival rate but it was not statistically significant (p>0.05). Investigating the frequency of tumor infiltrated CD4+ and CD8+ T lymphocytes indicated that the percentages of tumor infiltrated CD4+ T lymphocytes in response to structural and secreted proteins were higher compared to the control groups. CONCLUSION: Our study suggests that C. albicans structural and secreted proteins modulate intratumor T lymphocyte infiltration.

Evaluation the anti proliferative activity of structural proteins and fraction of supernatant from culture of Candida albicans.

In this study, anti proliferative activity of structural proteins and fraction of supernatant from culture of Candida albicans on proliferation responses of lymph node cells in Balb/c mice have been evaluated. For this reason Candida albicans was cultured in RPMI medium supplemented with 10% FBS at 37 in 5% CO2 until reaching a confluent state for 2 weeks. The culture supernatant was obtained by centrifugation and purified by gel filtration chromatography and structural proteins of C. albicans were obtained from breakage of cell wall by vortexing with glass beads in suspension of PBS and 1 mM PMSF and then cultured with lymph node cells and evaluated by MTT assay. The results in this study demonstrated that both of structural proteins and fraction of supernatant from culture of Candida albicans suppress immune responses compared with Control group. Our study provides evidence that proteins of C. albicans have anti proliferative activity.