Tehran University Medical Journal

Background: Nowadays, dendritic cells (DCs) have a special place in cancer treatment strategies and they have been used for tumor immunotherapy as they can induce immune response against tumor cells. Researchers have been trying to generate efficient dendritic cells in vitro therefore, this research was done to generate them for use in research and tumor immunotherapy.

Methods: This study took place at Urmia University in 2010-2011 years. In this study plastic adherent monocytes were incubated with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for five days. Finally, fully matured and stable DCs were generated by 48 hours of incubation in a monocyte conditioned medium (MCM) containing tumor necrosis factor-α (TNF-α) and epithelial cells. Phenotypic and functional analysis were carried out by using anti-CD14, anti-CD80, anti-CD86, and anti-CD83 monoclonal antibodies, and by determining their phagocytic activity, mixed lymphocyte reaction (MLR) and cytokine production, respectively.

Results: Dendritic cells were produced with high levels of surface molecule, i.e. of CD80, CD83, CD86, HLA-DR, expression and low levels of CD14 expression. Dendritic cells showed efficient phagocytosis and ability to stimulate T-lymphocytes. Moreover, dendritic cells could secrete high levels of interleukin-12 (IL-12) cytokine which was depictive of their full maturation. Measurement of the produced cytokines showed the generation of type-1 dendritic cells (DC1).

Conclusion: Our study showed that skin epithelial cells could induce maturation of monocyte-derived dendritic cells (DCs). This feeder layer led to the production of efficient dendritic cells with the ability to be used for tumor immunotherapy.

Background: Use of certain antipsychotic drugs has severe effects on fertility in males. Hypothalamus and hypophysial impressions and changes in plasma hormones concentration like prolactin, LH and FSH can affect sperm production. In this study, we investigated the effects of sulpiride on sperm quality, maturation and DNA damage.

Methods: Twenty for adult male mice (age: 6-8 weeks) were divided into three groups. The treatment group received 40 mg/kg sulpiride solution and the control sham group was given carrier of the drug intraperitoneally (IP) daily for 45 days but the control group received nothing. Finally, all the mice were sacrificed by cervical dislocation and their cauda epididymis were removed surgically. The excised specimens were placed in 1 ml HTF medium and incubated for 30 min in CO2 incubator to allow the spermatozoa to swim out. Later, sperm count, motility and viability were analyzed. Additionally, sperm chromatin quality and DNA integrity were assessed by aniline blue and acridine orange staining.

Results: Significant decrease in sperm motility and count were observed in the treatment group while the number of abnormal sperm increased as compared with the other two groups. Sperm viability and DNA maturation showed significant reduction and the rate of DNA damage increased in comparison with the control sham and the control groups (P<0.05).

Conclusion: The study showed that sulpiride has negative effects on sperm parameters in treated animals and in some cases it could cause secondary infertility.

Background: Multiple Sclerosis (MS) is an autoimmune disease with impairment in function of central nervous system. Macrophages and dendritic cells play important roles in alleviating or progression of the disease. These cells can cause inflammation and damage to the myelin of nerve cells by realizing of harmful substances when these cells get matured. We studied the effect of Alternaria alternata extract on maturation of monocyte- derived dendritic cell (modc) and T-cell responses in the presence of Myelin Basic Protein (MBP) as a laboratory model of multiple sclerosis (MS). The purpose of this study is suitable dendritic cells production for usage in MS immunotherapy.
Methods: For this study plastic adherent monocytes were cultured with granulocyte/ macrophage- colony stimulating factor (GM-CSF) and interleukin -4 for converting these cells to modc and pulsed with MBP and matured in the presence of monocyte-conditioned medium (MCM) in control group and MCM + Alternaria alternata extract in treatment groups. Anti-CD14, anti-CD83, anti-human leukocyte antigen-DR (anti HLA-DR) monoclonal antibody were carried out for phenotyping. Autologos T cell responses and cytokine production were evaluated.
Results: The results showed that the expression of CD14 decreased and CD83, HLA-DR increased in treatment groups in comparison with control groups. The production amount of IL-10 overcame IL-12 and in T cell the production of cytokines, IL-17 and Interferon-γ (IFN-γ) decreased and IL-4 was increased (P<0.05). These effects escalated with increasing of dosage from 50 to 100 (mg/ml) (P<0.001).
Conclusion: Alternaria alternata extract can cause maturation of MBP-pulsed modc and skewing of T- lymphocyte toward Th2 and thereby can evolve into a new strategy in immunotherapy of MS.