Modulation of the Culture Supernatant of Decidual Cells with Exogenous Cytokines on Killing Activity of Natural Killer Cells in Early Pregnancy

To investigate the important function of cytokines in early pregnancy and to provide basic and experimental evidence for understanding the mechanism of their action. Methods Add interferon γ(IFN γ),interleukin 2(IL 2), interleukin 6(IL 6) and epidermal growth factor(EGF) to the confluent culturing decidual cells with three different concentrations and harvest the culture supernatant after 12, 24 and 48 h separately. Observe the effect of the supernatant on killing activity of NK cells with radioimmunological assay of 51 Cr immersion. Results The culture supernatant of decidual cells can promote the killing activity of NK cells in various degrees, and the effect is independent of the type, concentration and acting time of cytokines. Conclusion In normal pregnancy, decidual cytokine network is in a dynamic equilibrium. Exogenous cytokines would be harm to normal pregnancy by interfering the equilibrium state, but the exact mechanism needs further study.

Secretion of immunoregulatory cytokines by mesenchymal stem cells

According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.

Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions

AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P < 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P < 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P < 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P < 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P < 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P <0.01,P < 0.001 and P < 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P < 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P < 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P < 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.

Effect of Cytokines Secreted by Human Adipose Stromal Cells on Endothelial Cells

Summary： To isolate and culture adipose stromal cells （ASCs）, and study the effect of cytokines secreted by ASCs on endothelial cells, human adipose tissue was digested with collagenase type Ⅰ solution and ASCs were derived by culture. The cells surface phenotype was examined by flow cytometry. ELISA was used to detect the secretion of VEGF, HGF, SDF- 1α and RT-PCR was employed to detect the expression of their mRNA. Then the ASC medium was utilized to culture human umbilical vein endothelial cells ECV304. Cells were counted by hemacytometer to determine the proliferation and Annexin V/ PI was employed for the examination of the apoptosis rate of ECV304. ASCs were derived by culture and expressed CD34, CD105 while they did not express CD31 or CD45. ASCs secreted cytokines such as VEGF, HGF and SDF-1α so the ASC medium could stimulate proliferation and counteract apoptosis of endothelial cells （P〈0.05）. Bcl-2 mRNA was also found to be up-regulated in the endothelial cells. It is concluded that ASCs can secrete cytokines and has significant effect on the proliferation of endothelial cells and apoptosis.

Effects of emodin on the proliferation of the glomerular mesangial cell and correlative cytokines in rats

Objective：To investigate the effects of emodin（EMD） on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods：The effects of EMD on cell proliferation and IL-6, TGF-β1 secretion of glomerular mesangial in rats were observed. Cell proliferation was measured by MTT method. IL-6 and TGF-β1 secretion was detected with ELISA. Results：EMD was able to inhibit the cell proliferation and down-regulate the IL-6 and TGF-β 1 secretion of glomerular mesangial, as compared to the model group in rats （P 〈 0.05）. Conclusion：EMD could significantly inhibit the cell proliferation, and reduce the creation of extracellular matrix（ECM）, this indicated that it could play an important role in alleviation and prevention of glomerular sclerosis. The mechanism may be that EMD can reduce the IL-6 and TGF-β1 secretion ofglomerular mesangial cell in rats.

Lethal effect of mononuclear cells derived from human umbilical cord blood differentiating into dendritic cells after in vitro induction of cytokines on neuroblastoma cells

BACKGROUND： Dendritic cell is the most major antigen presenting cell of organism. It is proved in recent studies that human umbilical cord blood mononuclear cells induced and cultured in vitro by recombinant human granulocyte-macrophage colony stimulating factor （rhG-MCSF） and recombinant human interleukin-4 （rhlL-4） can generate a great many dendritic cells and promote the lethal effect of T cells on human neuroblastoma, but it is unclear that whether the lethal effect is associated with the most proper concentration of dendritic cells. OBJEETIVE： To investigate the lethal effect of human umbilical cord blood mononuclear cells induced in vitro by cytokines differentiating into dendritic cells on human neuroblastoma, and its best concentration range. DESIGN ： Open experiment SEI-FING： Department of Pediatrics, the Medical School Hospital of Qingdao University MATERIALS ： The study was carried out in the Shandong Provincial Key Laboratory （Laboratory for the Department of Pediatrics of the Medical School Hospital of Qingdao University） during September 2005 to May 2006. Human umbilical cord blood samples were taken from the healthy newborn infants of full-term normal delivery during October to November 2005 in the Medical School Hospital of Qingdao University, and were voluntarily donated by the puerperas. Main instruments： type 3111 CO2 incubator （Forma Scientific, USA）, type 550 ELISA Reader （Bio-Rad, USA）. Main reagents： neuroblastoma cell line SK-N-SH （Shanghai Institute of Life Science, Chinese Academy of Sciences）, RPMI-1640 culture fluid and fetal bovine serum （Hyclone）, rhlL-4 （Promega, USA）, rhG-MCSF （Harbin Pharmaceutic Group Bioengineering Co.Ltd）, rat anti-human CDla monoclonal antibody and FITC-labeled rabbit anti-rat IgG （Xiehe Stem cell Gene Engineering Co.Ltd）. METHODS： ① Human umbilical cord blood mononuclear cells obtained with attachment methods differentiated into human umbilical cord blood dendritic cells, presenting typical morphology of dendritic cells after in vitro induction by rhG-MCSF and rhlL-4. ② Different concentrations of dendritic cells[ dendritic cells： neuroblastoma cells=20：1,50：1,100：1 （2×10^8 L^-1,5×10^8 L^-1,1×10^9 L^-1）], 1×10^9 L^-1 T cells and 1×10^7 L^-1 neuroblastoma cells were added in the experimental group. 1 ×10^9 L^-1 T cells and 1 ×10^7 L^-1 neuroblastoma cells were added in the control group. ③ Main surface marker CDla molecules of dendritic cells were detected with indirect immunofluorescence, and the percent rate of dendritic cells was counted with ultraviolet light and expressed as the expression rate of CD1a^＋ cells. ④Single effector cells and target cells were respectively set in the experimental group and control group to obtain the lethal effect. The lethal effect of dendritic cells on neuroblastoma cells was indirectly evaluated by detecting cellular survival with MTT assay. The lethal effect（%）= （1-A experimentat well-A effector cell /A target cell well）×100%.⑤The expenmental data were presented as Mean ±SD, and paired t test was used. MAIN OUTCOME MEASURES： ① Morphological characters of dendritic cells in the process of induction and differentiation. ②CD1a^＋ cellular expression rate. ③Lethal effect of dendntic cells on neuroblastoma cells. RESULTS： ①Morphological characters of dendritic cells in the process of induction and differentiation： On the 15^th day after human umbilical cord blood mononuclear cells were induced by rhG-MCSF and rhlL-4, typical morphology of dendritic cells could be seen under an inverted microscope. ②Expression rate of CD1a^＋ cells was （43.12±5.83）%. ③Lethal effect of dendritic cells on neuroblastoma cells： Lethal effect of dendritic cells stimulated T cells in each experimental group （ dendritic cells： neuroblastoma cells=100：1,50：1, 20：1 respectively） on neuroblastoma cells was significantly higher than that in control group[（31.00 ±4.41 ）%, （30.92±5.27）%,（33.57±5.35）%,（26.23±5.20）%, t=3.51,2.98,4.24, P〈 0.01 ）; But the lethal effect of dendntic cells on neuroblastoma was significantly lower when their ratio was 100：1 and 50：1 in comparison with 20：1 （t=2.01,2.36, P 〈 0.05）, and no significant difference in lethal effect existed between the ratio at 100：1 and 50：1 （t=0.06,P 〉 0.05）. CONCLUSION： Dendritic cells differentiated from human umbilical cord blood mononuclear cells after in vitro induction of cytokines can promote the lethal effect of T cells on neuroblastoma cells. The lethal effect is associated with the concentration of dendritic cells within some range.

Induced neuronal differentiation of neural stem cells by a combination of cytokines One-step versus two-step methods

BACKGROUND： A combination of basic fibroblast growth factor （bFGF）, platelet-derived growth factor （PDGF）, human heregulin-beta-1, beta-mercaptoethanol retinoic acid and forskolin has been reported to induce the differentiation of rat bone marrow stromal cells into myelinating Schwann-like cells. OBJECTIVE： To investigate the inducing effects of a combination of bFGF, PDGF, human heregulin-beta-1, beta-mercaptoethanol retinoic acid and forskolin on neural stem cell differentiation by one- and two-step methods. DESIGN, TIME AND SETTING： A cytobiology experiment was performed at the Department of Histology and Embryology, Medical School of Nantong University, and Jiangsu Province Key Laboratory of Neuroregeneration, China, between August 2005 and January 2007. MATERIALS： A total of 30 healthy Sprague Dawley rat embryos at gestational days 14-16 were selected, bFGF, PDGF, human heregulin-beta-t, beta-mercaptoethanol, retinoic acid, and forskolin were purchased from Sigma, USA. METHODS： Passage 3 rat neural stem cells were cultured by a one-step method in serum-free medium plus 10 ng/m/bFGF, 5 ng/mL PDGF, 200 ng/mL heregulin-beta-1,35 ng/mL all-trans retinoic acid, and 5 pmol/L forskolin or by a two-step method in serum-free medium plus 35 ng/m/ all-trans retinoic acid for 72 hours, followed by serum-free medium plus 10 ng/mL bFGF, 5 ng/mL PDGF, 200 ng/mL heregulin-beta-t and 5 μmol/L forskolin. The control condition consisted of 10% fetal bovine serum alone or 20 ng/mL bFGF alone. MAIN OUTCOME MEASURES： Differentiated cells were identified by immunocytochemical staining for microtubule associate protein-2 （MAP2） and St 00 protein. Geometric parameters and sodium ion currents of the differentiated cells were measured by image analysis and whole-cell patch-clamp techniques, respectively. RESULTS： Compared with the two-step culture method, neuronal-like cells exhibited longer processes and a similar appearance to mature neurons using the one-step method. The percentage of MAP2 positive cells induced by the one-step method was significantly greater than the serum-alone group （P 〈 0.05）. Furthermore, the MAP2 positive cells induced by the one-step method had greater surface areas, cell body perimeters, and longer process than cells induced by serum-alone and bFGF-alone （P 〈 0.05）. There were no significant differences in these parameters between the one-step and two-step methods （P 〉 0.05）. In addition, 80% of the induced neuronal-like cells from the one-step method and 20% from the two-step method displayed inwardly-evoked currents. CONCLUSION： The combination of bFGF, PDGF, human heregulin-beta-t, beta-mercaptoethanol retinoic acid and forskolin successfully induced neuronal differentiation from neural stem cells, with the one-step induction being more effective than the two-step method.

Cytokines Released from Allergen-Stimulated Blood Cells during the Delayed Asthmatic Response to Allergen Challenge

Background: Bronchial asthma patients may develop various asthmatic response types to bronchial challenge with allergen, such as immediate (IAR), late (LAR), dual (DAR) or delayed (DYAR), due to different immunologic mechanisms. The DYAR, beginning between 26-32 hrs and lasting up to 56 hrs after the allergen challenge, differs from the IAR, LAR and DAR in clinical, diagnostic and immunologic aspects. The aim of this study was to investigate the concentrations of the particular intracellular cytokines released by blood cells stimulated with relevant allergens “in vitro”, before and during the DYAR. Methods: In 23 patients, the repeated DYAR (p < 0.001) was supplemented with cytokine determination in the supernatants of the blood cells stimulated with relevant allergens before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results: The significantly elevated pre-challenge concentrations (p < 0.05) of IL-2, IL-17, IFN-γ and G-CSF released by allergen-stimulated blood cells “in vitro” were recorded in the DYAR patients as compared with healthy controls. The significantly increased post-challenge concentrations (p β, IL-2, IL-8, IL-12p70, IL-18, IFN-γ and TNF-α, whereas decreased concentrations of IL-4, IL-6 and IL-17, were released by blood cells stimulated with relevant allergens “in vitro”, as compared both with their pre-challenge concentrations and with the corresponding PBS control values. Conclusions: The profiles of cytokines released by allergen-stimulated peripheral blood cells during the DYAR would suggest an activation of Th1 cells, neutrophils, monocytes and probably also bronchial macrophages, epithelial and endothelial cells and their involvement in the immunologic mechanism(s) underlying the clinical DYAR.

Effects of Chemotherapy on Peripheral Blood NK Cell Receptor NKG2D and Related Immune Cytokines in Patients with Non-Small Cell Lung Cancer

Objective: To analyze the effect of chemotherapy on peripheral blood NK cell receptor NKG2D and related immune cytokines (IL-12, IL-15, IL-18) in patients with non-small cell lung cancer (NSCLC). Methods: A total of 48 patients with NSCLC who visited the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2019 were selected as the study subjects. Changes in the expression levels of NKG2D, IL-12, IL-15 and IL-18 in peripheral blood of patients at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed to investigate the correlation between NKG2D and IL-12, IL-15 and IL-18 in peripheral blood at each time point. Results: The expression levels of NKG2D, IL-15, and IL-18 in the peripheral blood of the patient before chemotherapy, after the first chemotherapy, and after the second chemotherapy gradually decreased. After the first chemotherapy and the second chemotherapy, the peripheral blood IL-12 was significantly lower than before chemotherapy, and IL-12 in peripheral blood after the second chemotherapy was slightly increased compared with that after the first chemotherapy. The comparison of each factor at different time points was statistically significant (all P<span style="font-family: ">0.05). Pearson correlation analysis showed that after the first chemotherapy, NKG2D in peripheral blood was positively correlated with IL-18 (r = 0.342, P = 0.031);after the second chemotherapy, NKG2D in peripheral blood was positively correlated with IL-18 (r = 0.411, P = 0.023), negatively correlated with IL-15 (r = -0.451, P = 0.001). Conclusion: There was no significant change in the number of NK cells in the peripheral blood of NSCLC patients after chemotherapy, while NKG2D and related immune cytokines decreased, which may be one of the mechanisms for the suppression of immune function in patients, and this provides a potential target for immunotherapy in patients.

Prognostic Value of Th-22 Cells and Related Functional Cytokines in Patients with Vitiligo

Objective:To investigate the prognostic value of Th-22 cells and related functional cytokines in patients with vitiligo.Methods:Thirty-five patients with vitiligo who admitted to the outpatient clinic from June 2016 to November 2018 in the hospital were selected as the study group.Thirty healthy controls were selected as the control group.Th-22 cells and their related cytokines were analyzed in both groups.Resylts:The levels of cytokines in Th-22 and Th-17 cells in the study group were significantly higher than those in the control group(P<0.05).The expression of Treg lymphocyte-related factors in the study group was lower than that in the control group(P<0.05).The changes in cell and factor levels in patients with vitiligo before and after treatment were significantly different(P<0.05).Conclusion:It is shown that three cells,including Th-22,Th-17 and Treg are related to each other,and they can inhibit and promote the pathogenesis of vitiligo which provides a reference for prognosis and treatment.

Effect of Chemotherapy on Peripheral Blood DC Cells and Related Immune Cytokines in Patients with Non-Small Cell Lung Cancer

Objective: To analyze the effects of chemotherapy on peripheral blood DC cells and related immune cytokines (NKG2D, DC cells, TNF-a, IFN-r, HMGB-1) in patients with non-small cell lung cancer (NSCLC). Methods: Ninety-five NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to February 2021 were selected as the research objects, and the changes in the expression levels of DC cells, NKG2D, TNF-a, IFN-r, HMGB-1 in the peripheral blood of patients at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy) were analyzed, and the correlation between DC cells in blood and NKG2D, TNF-a, IFN-r, HMGB-1 at each time point was explored. Results: The expression levels of NKG2D, TNF-a, IFN-r, and HMGB-1 in the peripheral blood of the patient before chemotherapy, after the first chemotherapy, and after the second chemotherapy gradually decreased, and there was no significant change in DC cells, except for DC cells at different times. The difference between each factor of each point was statistically significant (all P < 0.05). Pearson correlation analysis showed that there was no correlation between peripheral blood DC cells of patients at different time points and other factors. Conclusion: The decrease of other immune cytokines except DC cells in peripheral blood of patients with NSCLC after chemotherapy may be one of the mechanisms by which the patient’s immune function is suppressed. There is no correlation between DC cells and other factors.

Effect of acupuncture on acupoint "Yingxiang-Hegu" on Th1, Th2 cytokines and T-bet/GATA-3 of allergic rhinitis rats

Objective:To explore the effect of"Yingxiang-Hegu"on Th1,Th2-related cytokines and[2]transcription factors T-bet and GATA-3 in rats with allergic rhinitis.Methods:Rats were randomly divided into three groups:blank group,model group and acupoint group.The rat model of ovalbumin(OVA)AR was established,and the general condition of the rats was observed and scored.Acupuncture intervention was performed on the acupoint group on the second day after successful modeling,once per day for 20 min for 10 d.After intervention,the general behavior,behavioral score and histomorphological changes of nasal mucosa were observed.Eosinophils(EOS)were counted under microscope after nasal lavage smear staining,and the contents of total IgE,IFN-γ,IL-12,IL-4 and IL-5 in serum were detected by ELISA.Westernblot and IHC were used to detect the protein level and positive protein expression of specific transcription factors T-bet and GATA-3 in rat nasal mucosa.Results:After the establishment of the model,except for the blank group,the behavioral observation scores of rats in the model group and acupoint group were more than 5 points,indicating that the model was successful.After acupuncture intervention on acupoint"Yingxiang-Hegu",the behavioral score of rats in the acupoint group and western medicine group was significantly lower than that in the model group(P<0.05).Microscopic examination showed that the structure of nasal mucosa in the model group was obviously damaged,cilia were arranged discontinuously,uneven,local congestion and swelling,a large number of epithelial cells exfoliated and necrotic,goblet cell proliferation,obvious inflammatory cell infiltration.The pathological degree of nasal mucosa in the pair point group was significantly less than that in the model group.Compared with the model group,the levels of IFN-γ,IL-2 and IL-12 in serum were significantly increased,while IgE,IL-4,IL-5 and IL-6 were significantly decreased,GATA-3 protein and positive expression in nasal mucosa were significantly decreased and T-bet was significantly increased after acupuncture.Conclusion:Acupuncture at"Yingxiang-Hegu"can effectively improve the nasal sensitive symptoms and control nasal inflammation in AR rats.The mechanism may be that acupuncture at Yingxiang-Hegu can up-regulate the expression of T-bet,decrease the level of GATA-3,promote the production of Th1 cytokines and inhibit the synthesis and secretion of Th2 cells,thus restoring the immune balance of Th1 and Th2.

The Effectof BCG-PSN on T-cell Subsets and Cytokines in Vernal Conjunctiviti

The effects of BCG PSN on T cell subsets and cytokines in vernal conjunctivitis were observed. The level of total IgE was quantitatively determined before and after treatment with BCG PSN by allergen diagnostic instrument in vitro . The content of T cell subsets of peripheral blood and cytokine were determined by using indirect immune fluorescence method, and IL 4 and INF γ were quantified by ELISA. The results showed that the level of total IgE was substantially reduced ( P <0.01) after treatment in the BCG PSN group. Meanwhile, CD + 8 was decreased, CD + 4 and CD + 4/CD + 8 ratio elevated with significant differences ( P <0.05) as compared with pre treatment results. The changes in total IgE, CD + 8 ,CD + 4 and CD + 4/CD + 8 ratio after treatment also presented significant differences ( P <0.05) between BCG PSN group and routine treatment group. The level of IL 4 in serum declined ( P <0.05) after treatment in the BCG PSN group, and INF γ went up ( P <0 05). IL 4 and INF γ in serum showed significant differences ( P <0.05) between two groups after treatment. It is concluded that BCG PSN has a bi directional immunoregulating effect. It can bring CD + 4 and CD + 8 into homeostasis, thereby preventing the occurrence of anaphylaxis. At the same time, BCG PSN can restrain Th 2, decrease the synthesis of IL 4, switch the balance of Th l/Th 2 to Th 1 side, boost up the predominance of Th 1 relatively, which is propitious to perennial stabilization and recovery of vernal conjunctivitis.

Proliferation and Apoptosis of Bone Marrow CD4^+ T Cells in Patients with Aplastic Anemia and Impacts of the Secreted Cytokines on Hematopoietic Stem Cells from Umbilical Cord Blood

Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy con...

Effects of cytokines and chemokines on migration of mesenchymal stem cells following spinal cord injury

We investigated the effects of cytokines and chemokines and their associated signaling pathways on mesenchymal stem cell migration after spinal cord injury, to determine their roles in the curative effects of mesenchymal stem cells. This study reviewed the effects of tumor necrosis factor-α, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, basic fibroblast growth factor, insulin like growth factor-I, stromal cell-derived factor and monocyte chemoattractant protein-1, 3 during mesenchymal stem cell migration to damaged sites, and analyzed the signal transduction pathways involved in their effects on mesenchymal stem cell migration. The results confirmed that phosphatidylinositol 3-kinase/serine/threonine protein kinases and nuclear factor-KB play crucial roles in the migration of mesenchymal stem cells induced by cytokines and chemokines.

Effects of Ginkgo Leaf Extract on Function of Dendritic Cells and Th1/Th2 Cytokines in Patients with Unstable Angina Pectoris

Objective： To investigate the effects of Ginkgo leaf extract （GLE） on function of dendritic cells （DO） and Th1/Th2 cytokines in patients with unstable angina pectoris（UAP）. Methods： Fifty-four patients with UAP were equally assigned into two groups, the treated group and the control group, both treated with conventional Western medicine, but with GLE given additionally to the treated group. Blood of all patients was taken before and 4 weeks after treatment to prepare the peripheral mononuclear cells, then which were incubated in the completed medium containing granulocyte-macrophage colony stimulatory factor （GMCSF） and interleukin-4 （IL-4） to induce mature DO. The expression of co-stimulating factor CD86 （B7-2） on the surface of DC was detected by flow cytometry, and the stimulating capacity of DC was determined by mixed lymphocyte reaction （MLR）. The blood levels of cytokines, interferon-γ （IFN-γ）, and IL-4, were analyzed by ELISA, and blood C-reactive protein （CRP） level by turbidimetry. Moreover, the direct effect of Ginkgolide B on CD86 expression on DO were also tested in vitro. Results： After treatment, CD86 expression on DO, the stimulating capacity of DO as well as levels of IFN-γ and ORP were lowered in both groups （P〈0.05 or P〈0.01）, but the changes were much more significant in the treated group than those in the control group. Ginkgolide B showed a direct inhibitory effect on the CD86 expression on DO. Conclusion： The inhibition of GLE on DO and thereby the suppression on inflammatory reaction may be one of the mechanisms of GLE in treating patients with UAP.

Cytokines in adipose-derived mesenchymal stem cells promote the healing of liver disease

Adipose-derived mesenchymal stem cells(ADSCs) are a treatment cell source for patients with chronic liver injury. ADSCs are characterized by being harvested from the patient's own subcutaneous adipose tissue, a high cell yield(i.e., reduced immune rejection response), accumulation at a disease nidus, suppression of excessive immune response, production of various growth factors and cytokines, angiogenic effects, antiapoptotic effects, and control of immune cells via cellcell interaction. We previously showed that conditioned medium of ADSCs promoted hepatocyte proliferation and improved the liver function in a mouse model of acute liver failure. Furthermore, as found by many other groups, the administration of ADSCs improved liver tissue fibrosis in a mouse model of liver cirrhosis. A comprehensive protein expression analysis by liquid chromatography with tandem mass spectrometry showed that the various cytokines and chemokines produced by ADSCs promote the healing of liver disease. In this review, we examine the ability of expressed protein components of ADSCs to promote healing in cell therapy for liver disease. Previous studies demonstrated that ADSCs are a treatment cell source for patients with chronic liver injury. This review describes the various cytokines and chemokines produced by ADSCs that promote the healing of liver disease.

Cytokines as critical co-stimulatory molecules in modulating the immune response of natural killer cells

Cytokines 涉及指导生来的杀手(NK ) 的激活房间。NK 房间涉及被改变了的房间的识别；因此，他们不认出特定的侮辱到主人，但是当激活时，能够直接破坏感染的房间，以及由 cytokines 和 chemokines 的版本支持免疫系统的另外的部件的招募和反应。是这些性质使 NK 房间成为了天生的免疫和适应免疫的关键部分。

The expression of CD40 and CD40L on the surface of peripheral blood mononuclear cells in asthmatic rats and the effect of anti-CD40L McAb on Th1 and Th2 cytokines

Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Methods： Flow cytometry and RT-PCR were used to detect the expression of CD40 and CD40L of PBMCs in asthmatic rats. After the PBMCs was treated with anti-CD40L McAb, ELISA was used to detect the IL-4 and IFN-γ levels of culture supernatants. Results： Compared with the normal control group, the expression of CD40 and CD40L of PBMCs in asthmatic rats increased （P 〈 0.05）. Compared with the untreated group, the level of IL-γ and the ratio of IL-4/IFN-γ decreased after the PBMCs was treated with anti-CD40L McAb（P 〈 0.05）. Conclusion： The expression of CD40 and CD40L on the surface of PBMCs in asthmatic rats was up-regulated. Anti-CD40L McAb can rectify the imbalance of Th1 and Th2 cytokines.