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.

Effect of JIANPI HUOXUE decoction on inflammatory cytokine secretion pathway in rat liver with lipopolysaccharide challenge

AIM： To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction （JHD） on cytokine secretion pathway in rat liver induced by lipopolysaccharide （LPS）. METHODS： Twenty-four male SD rats were divided into normal group （n = 4）, model group （n = 10） and JHD group （n = 10） randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 μg/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylineosin （H.E.） staining. Tumor necrosis factor alpha （TNF-α） in serum were assayed by enzyme linked immunosorbent assay （ELISA）. The protein expression of TNF-α, phosphorylated inhibit-κB （p-κB） and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-α, interleukin-6 （IL-6）, CD14, toll-like receptor 2 （TLR2） and TLR4 in liver were assayed by real-time RT-PCR.RESULTS： Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-α （31.35 ± 6.06 vs 12225.40 ± 9007.03, P 〈 0.05）, protein expression of CD68 （1.13 ± 0.49 vs 3.36 ±1.69, P 〈 0.05）, p-IκB （0.01 ±0.01 vs 2.07 ＋ 0.83, P 〈 0.01） and TNF-α （0.27 ± 0.13 vs 1.29 ± 0.37, P 〈 0.01） in liver and mRNA expression of TNF-α （1.96 ± 2.23 vs 21.45 ±6.00, P 〈 0.01）, IL-6 （4.80 ± 6.42 vs 193.50 ± 36.36, P 〈 0.01） and TLR2 （1.44 ± 0.62 vs 4.16 ± 0.08, P 〈 0.01） in liver were also increased significantly. These pathological changes were all improved in .1HD group. On the other hand, TLR4 mRNA （1.22 ± 0.30 vs 0.50 ± 0.15, P 〈 0.05） was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation. CONCLUSION： JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IκB and endotoxin receptor TLR2.

Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

This study investigated whether bone marrow mesenchymal stem cell（BMSC） transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs（h BMSCs） were injected into the tail vein. Fourteen days later, we found that h BMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor（s EPOR） was injected into the lateral ventricle, and on the next 13 consecutive days. s EPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the h BMSCs ＋ s EPOR group than in the h BMSCs ＋ heat-denatured s EPOR group. The adhesive-removal test result and the modified Neurological Severity Scores（m NSS） were lower in the h BMSCs ＋ s EPOR group than in the heat-denatured s EPOR group. The adhesive-removal test result and m NSS were similar between the h BMSCs ＋ heat-denatured s EPOR group and the h BMSCs ＋ s EPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.

Clinical study of co-treatment with DC-CIK cells for advanced solid carcinomas

Objective： The aim of this study was to observe the therapeutic effect of cytokine induced killer （CIK） cells in combination with dendritic cells （DCs） on advanced solid carcinoma patients. Methods： Isolated peripheral blood mononuclear cells （PBMCs） from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor （GM-CSF）, tumor necrosis factor-a （TNF-a） and interleukin-4 （IL-4） to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-y （IFN-y）, interleukin-2 （IL-2） and CD3 monoclonal antibody （CD3 McAb） to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results： Forty-two patients with measurable nidus, 2 achieved complete remission （CR）, 9 partial remission （PR） and 15 stable disease （SD）, while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion： DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.

The HMGB1 signaling pathway activates the inflammatory response in Schwann cells

Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1（HMGB1）, is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products（RAGE）, but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.

Effect of polysaccharide sulfate 916 on the production of nitric oxide in ECV3 04 cells induced by cytokines and H_2O_2

To investigate the effect of polysaccharide sulfate 916 (PS916) on the productio n of nitric oxide (NO) in ECV304 cells induced by tumor necrosis factor α (TNF α), interleukin 1β (IL 1β) and H 2O 2 in vitro Methods Production of NO in ECV304 cells was measured by the Griess method and the proli feration of cells was tested by the MTT method The activity of NO synthase was detected spectrophotometrically Results Production of NO in ECV304 cells decreased after treatment with 40?ng/ml IL 1 β and 40?ng/ml TNFα, but increased in the presence of H 2O 2 0 1?mmol/L PS916 significantly enhanced NO production in ECV304 cells in a dose depende nt manner in the TNFα and IL 1β treated groups and decreased it in the H 2O 2 treated group Proliferation of ECV304 cells was inhibited by TNFα and H 2O 2 and no effect was found in the IL 1β treated group PS916 increased the proliferation of cells treated with TNFα and H 2O 2 dose dependently In vitro, PS916 has no effect on the activity of NO synthase Conclusion PS916 has a protective effect on ECV304 cells exposed to IL 1β, TNFα and H 2 O 2

Inhibition of lovastatin on proliferation and expression of promflammatory cytokines in cultured human glomerular mesangial cells

Objective To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells.Methods The influence of lovastatin on HMC proliferation was evaluated with 3H-thymidine incorporation. mRNA expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1) and activation of NF-KB of HMC were measured using Reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA) respectively.Results Lovastatin was found to have inhibitory effects on human mesangial cell (HMC) proliferation and lipopolysaccharide ( LPS )-mediated human mesangine cell HMC mRNA expression of proinflammatory cytokines via activation of NF-KB. The effect of lovstatin on HMC could be prevented when the mevalonate and farnesol were added to the culture.Conclusion Lovastatin may decrease HMC proliferation and production of proinflammatory cytokines through the inhibition of NF-KB activation. This provided experimental evidence for further evaluation of the renal protective effect of HRI, suggesting that it may be a potent agent for prevention of progressive reanl diseases aside from its lipid-lowering effect.

Time-dependent gene expression analysis after mouse skeletal muscle contusion

Background:Though the mechanisms of skeletal muscle regeneration are deeply understood,those involved in muscle contusion,one of the most common muscle injuries in sports medicine clinics,are not.The objective of this study is to explore the mechanisms involved in muscle regeneration after contusion injury.Methods:In this study,a total of 72 mice were used.Eight of them were randomly chosen for the control group,while the rest were subjected to muscle contusion.Subsequently,their gastrocnemius muscles were harvested at different time points.The changes in muscle morphology were assessed by hematoxylin and eosin(HE) stain.In addition,the gene expression was analyzed by real-time polymerase chain reaction.Results:The data showed that the expression of many genes,i.e.,specific markers of immune cells and satellite cells,regulatory factors for muscle regeneration,cytokines,and chemokines,increased in the early stages of recovery,especially in the first 3 days.Furthermore,there were strict rules in the expression of these genes.However,almost all the genes returned to normal at 14 days post-injury.Conclusion:The sequence of immune cells invaded after muscle contusion was neutrophils,M1 macrophages and M2 macrophages.Some CC(CCL2,CCL3,and CCL4) and CXC(CXCL10) chemokines may be involved in the chemotaxis of these immune cells.HGF may be the primary factor to activate the satellite cells after muscle contusion.Moreover,2 weeks are needed to recover when acute contusion happens as used in this study.

Dynamic Changes of Phenotypes and Secretory Functions during the Differentiation of Pre-DCs to Mature DCs

The dynamic expression of cytokines and phenotypes during the differentiation process of dendritic cell precursors（pre-DCs） to mature dendritic cells（DCs） was investigated,and the effects of inflammatory stimulation with lipopolysaccharide（LPS） on DCs differentiation were understood.The differentiation of bone marrow cells isolated from Balb/c mice was induced to DCs in an 8-day cell culture system with RPMI-1640 complete culture medium containing 10% FBS,20 ng/mL recombinant mouse granulocyte-macrophage colony-stimulating factor（rm GM-CSF） and 10 ng/m L recombinant mouse interleukin-4（rm IL-4）.On the day 3,6 and 7 after culture,DCs were divided into non-LPS group and LPS group,given 500 ng/m L LPS for 24 h stimulation and no stimulation respectively.The expression levels of CD11c~＋,MHC-Ⅱ~＋,CD40~＋,CD80~＋ and CD86~＋ were detected by flow cytometry,and those of IL-2,IL-4,IL-10,IL-12 p70 and IFN-γ in the supernatant by ELISA.On the day 3 and 6 after culture,the expression of IL-2,IL-4,IL-10 and IFN-γ in DCs showed no significant differences between non-LPS group and LPS group,whereas the differences were significant at day 7.The expression levels of cytokines（for IL-2,IL-4,IL-10,IFN-γ and IL-12 p70：152.86±6.91,778.33±8.35,44.55±2.54,58.26±1.09 and 2423.00±57.21 pg/mL respectively） in LPS group were higher than those in non-LPS group,especially IL-12 p70 increased obviously at day 7.It was concluded that during the differentiation process of pre-DCs to mature DCs,LPS stimulates DCs producing large amounts of IL-12 p70 and Th1-type cytokines as compared with Th2-type cytokines,and day 7 may be a key time-point for DCs polarization.

Cytokine expression of T cells in chronic myeloid leukemia

Objective To evaluate the function of T cells in chronic myeloid leukemia (CML) Methods Interleukin 1β (IL 1β), interleukin 2 (IL 2), interleukin 3 (IL 3), interleukin 4 (IL 4), interleukin 6 (IL 6), tumor necrosis factor alpha(TNFα), and granulocyte macrophage colony stimulating factor (GM CSF) gene expressions were investigated by reverse transcription polymerase chain reaction (RT PCR) assay in fluorescence active cell sorter (FACS) sorted peripheral blood CD2+/CD56 T cells from 12 CML patients, 10 meylodysplastic syndrome (MDS) patients and 7 normal individuals Results TNFα mRNA was transcribed in T cells from all of the CML, MDS and normal individuals IL 1β mRNA was transcribed in T cells from 10 CML, 9 MDS and 6 normal individuals Low levels of IL 2 and IL 4 mRNA were detected in 5 CML patients IL 3, IL 6 and GM CSF mRNA were undetectable in all samples Conclusion IL 4 and IL 2 were expressed abnormally in T cells of CML

Effect of polysaccharide sulfate 916 on the production of nitric oxide in ECV3 04 cells induced by cytokines and H2O2

To investigate the effect of polysaccharide sulfate 916 (PS916) on the productio n of nitric oxide (NO) in ECV304 cells induced by tumor necrosis factor α (TNF α), interleukin 1β (IL 1β) and H 2O 2 in vitro Methods Production of NO in ECV304 cells was measured by the Griess method and the proli feration of cells was tested by the MTT method The activity of NO synthase was detected spectrophotometrically Results Production of NO in ECV304 cells decreased after treatment with 40?ng/ml IL 1 β and 40?ng/ml TNFα, but increased in the presence of H 2O 2 0 1?mmol/L PS916 significantly enhanced NO production in ECV304 cells in a dose depende nt manner in the TNFα and IL 1β treated groups and decreased it in the H 2O 2 treated group Proliferation of ECV304 cells was inhibited by TNFα and H 2O 2 and no effect was found in the IL 1β treated group PS916 increased the proliferation of cells treated with TNFα and H 2O 2 dose dependently In vitro, PS916 has no effect on the activity of NO synthase Conclusion PS916 has a protective effect on ECV304 cells exposed to IL 1β, TNFα and H 2 O 2

Repressor of GATA-3 can negatively regulate the expression of T cell cytokines through modulation on inducible costimulator

Background The transcription factor, repressor of GATA-3 （ROG）, can simultaneously suppress the expression of T helper cells （Thl and Th2） cytokines. Since the suppression of Th2 cytokines by GATA-3 is well understood, it is postulated that there are other molecular targets of ROG that can suppress the expression of the Thl cytokines. We hypothesized that ROG might suppress the stimulators of T lymphocyte cytokines such as CD3, CD28, and inducible costimulator （ICOS）, or indirectly enhance the expression of cytokine suppressors such as T lymphocyte-associated antigen-4 （CTLA-4） and CD45. The objective of this study was to clarify the molecular targets of ROG involved in suppressing Thl or Th2 cytokines. Methods Real-time quantitative PCR （RT-PCR） and Western blotting were performed to evaluate the mRNA and protein levels of CD3, CD28, ICOS, CTLA-4, and CD45 in Thl and Th2 cells during various levels of ROG expression. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interferon-y （IFN-y） and intedeukin （IL）-4 in culture media of Thl and Th2 cells. Results The results showed that the mRNA and protein levels of ROG were relatively low in Thl and Th2 cells （P 〈0.01）. After ROG-pcDNA3.1 transfection, the mRNA and protein level of ROG was significantly elevated, while the expression of ICOS, IFN-y, and IL-4 was markedly down-regulated （P 〈0.01）. Conversely, transfection of ROG-siRNA led to inhibition of ROG expression and up-regulation of ICOS, IFN-y and IL-4 （P 〈0.01）. However, the expression levels of CD3, CD28, CTLA-4 and CD45 did not change in either ROG-pcDNA3.1 or ROG-siRNA-transfected Thl and Th2 cells （P 〉0.05）. Conclusion It is concluded that ROG can inhibit the expression of Thl and Th2 cytokines by down-regulating the expression of ICOS, which might be a potential molecular target for asthma treatment.

Pre-treatment with bone marrow-derived mesenchymal stem cells inhibits systemic intravascular coagulation and attenuates organ dysfunction in lipopolysaccharide-induced disseminated intravascular coagulation rat model

Background Bacterial lipopolysaccharide （LPS） can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation （DIC） during infection. In recent years, it has been found that bone marrow-derived mesenchymal stem cells （BMSCs） can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines. Here, we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism. Methods Forty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group. In the treatment groups, 0, 1×10^6, 2×10^6, 3×10^6, and 5×10^6 of BMSCs were injected intravenously for 3 days before LPS injection, while the control group was treated with pure cell culture medium injection. Then, the LPS （3 mg/kg） was injected via the tail vein in the treatment groups, while the control group received 0.9% NaCI. Blood was withdrawn before and 4 and 8 hours after LPS administration. The following parameters were monitored： platelets （PLT）, fibrinogen （Fib）, D-dimer （D-D）, activated partial thromboplastin time （APTT）, prothrombin time （PT）, tumor necrosis factor-a （TNF-（a）, interferon-y （IFN-a）, interleukin-1β （IL-1β）, creatinine （Cr）, alanine aminotransferase （ALT）, creatinine kinase-MB （CK-MB）, and endothelin （ET）. Results Compared with the control group, a significant change of coagulation parameters were found in the experimental groups. The plasma level of the inflammatory mediator （TNF-a, IFN-7, IL-1β）, organ indicator （Cr, ALT, and CK-MB）, and ET in the experimental groups were much lower （P〈0.05） than that in the control group. Furthermore, some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups （from group 2 to group 5） showed a significant difference （P 〈0.05）, except the ALl and CK-MB levels （P 〉0.05）. Conclusion Pre-treatment with BMSCs can attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune cells and proinflammatory cytokines in LPS-induced DIC rat model.

Comparison of mesenchymal stem cells from human placenta and bone marrow

Background Nowadays bone marrow represents the main source of mesenchymal stem cells (MSCs). We identified a new population of MSCs derived from human placenta and compared its biological characterization with bone marrow derived MSCs.Methods Mononucleated cells (MNC) were isolated from the human placenta tissue perfusate by density gradient fractionation. Individual colonies were selected and cultured in tissue dishes. At the same time,human bone marrow derived MSCs were identified. Culture-expanded cells were characterized by immune phenotyping and cultured under conditions promoting differetiation to osteoblasts or adipocytes. The hematopoietic cytokines were assayed using reverse transcriptase polymerase chain reaction (RT-PCR). Results Human placental MSCs exhibited fibroblastoid morphology. Flow cytometric analyses showed that the placental MSC were CD29,CD44,CD73,CD105,CD166,HLA-ABC positive; but were negative for CD34,CD45,and HLA-DR. Functionally,they could be induced into adipocytes or osteocytes. Moreover,several hematopoietic cytokine mRNA was found in placenta-derived MSCs by RT-PCR analysis,including IL-6,M-CSF,Flt3-ligand and SCF. These results were consistent with the properties of bone marrow derived MSCs.Conclusion These observations implicate the postpartum human placenta as an important and novel source of multipotent stem cells that could potentially be used for investigating mesenchymal differentiation and regulation of hematopoiesis.

Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation

Studies of wild animals’immunity often use comparison with laboratory-raised individuals.Using such an approach,various data were obtained concerning wild Norway rat’s immunity.Lower or higher potential of immune system cells to respond to activation stimuli were shown,because of analysis of disparate parameters and/or small number of analyzed individuals.Inconsistent differences between laboratory and wild rats were shown too,owing to great response variability in wild rats.We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment.To test this,we analyzed the circulating levels of inflammatory cytokine interleukin-6(IL-6),a mediator which has a central role in host immune defense.In addition,we examined the activity of the central immune organ,the spleen,including cell proliferation and production of pro-inflammatory cytokines interferon-γ(IFN-γ)and interleukin-17(IL-17),which are major effectors of cellular adaptive immune response.In order to obtain reasonable insight into the immunity of wild Norway rats,analysis was conducted on a much larger number of individuals compared to other studies.Higher levels of plasma IL-6,higher spleen mass,cellularity and basal IFN-γproduction concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10(IL-10)revealed more intense immune activity in the wild compared to laboratory rats.However,lower responsiveness of their spleen cells’proinflammatory cytokine production to concanavalin A(ConA)stimulation,along with preserved capacity of IL-10 response,might be perceived as an indication of wild rats’reduced capability to cope with incoming environmental stimuli,but also as a means to limit tissue damage.

Research on airway inflammation: present status in China's Mainland

Airway inflammation involving activated eosinophils, mast cells and T lymphocytes is an established feature of asthma and has been the key target to treatment. Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. These findings are documented in studies reaching back more than 20 years. However, among investigators concerning on asthma, airway inflammation and subsequent remodeling as a target of investigation was hardly a blip on the radar screen until a few years ago. Now the subject is of expanding concern to respiratory researchers of many stripes and persuasions, as judged by the rapid rise in the number of publications. Symposia, workshops, lectures, reviews, and grant proposal on this subject also are surging.This review will not attempt to provide a comprehensive description of all aspects of airway inflammation. Rather, it will focus on current data studied by Chinese researchers in the last few years, in which the depth and scope of the discussions were much more profound than before.

Subcutaneous administration of granulocyte colony stimulating factor and stem cell factor ameliorates the outcome of acute myocardial infarction

Orlic et al treated mice （splenectomized two weeks ago） with granulocyte colony stimulating factor （G-CSF） and stem cell factor （SCF） for five days before acute myocardium infarction （AMI） and three days after AMI. They found that those treatments could repair infarcted hearts, improve heart performance and decrease mortality. However, from the clinical standpoint, the work of Orlic and his co-workers has an obvious limitation.