1.Effects of recombinant fusion protein interleukin-18 on expression of immune-inflammatory factors in mice infected with Staphylococcus aureus.
Chen CHEN ; Qiang CHEN ; Lan LI ; Xiao-Jun YU ; Jiang-Wei KE ; Mei-Juan HE ; Hong-Ping ZHOU ; Wen-Ping YANG ; Wen-Xing WANG
Chinese Journal of Contemporary Pediatrics 2017;19(6):705-711
OBJECTIVETo observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo.
METHODSA total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2β mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR.
RESULTSCompared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2β mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ.
CONCLUSIONSIn the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.
Animals ; Chemokine CCL3 ; analysis ; Female ; Granulocyte Colony-Stimulating Factor ; blood ; Interferon-gamma ; blood ; Interleukin-18 ; therapeutic use ; Interleukin-4 ; blood ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; pharmacology ; therapeutic use ; Staphylococcal Infections ; drug therapy ; immunology
2.Therapeutic Effect of Combined Cytokines on Nonhuman Primate Model of Severe Haemopoietic Acute Radiation Sickness.
Yan-Chao MA ; Ming LI ; Shuang XING ; Guo-Lin XIONG ; Xing SHEN ; Qiu CHEN ; Yu-Wen CONG ; Jin-Xiang WANG ; Nan-Kang ZHU ; Zu-Yin YU ; Xue-Guang ZHANG
Journal of Experimental Hematology 2016;24(2):573-579
OBJECTIVETo evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment.
METHODSSeventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation.
RESULTSAfter 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated.
CONCLUSIONrhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.
Animals ; Bone Marrow ; pathology ; Bone Marrow Cells ; pathology ; Gamma Rays ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoiesis ; drug effects ; Hematopoietic Stem Cells ; cytology ; Humans ; Interleukin-2 ; pharmacology ; Macaca mulatta ; Radiation Injuries ; drug therapy ; Random Allocation ; Recombinant Proteins ; therapeutic use ; Thrombopoietin ; pharmacology ; Whole-Body Irradiation
3.Heparin-treated dendritic cells promote Th0 to Th1 differentiation via the Toll-like receptor 3 in peripheral blood monocytes of patients with chronic hepatitis B.
Weihong SUN ; Xiaofang WEI ; Peng ZHAO ; Airong NIU ; Changyou LI ; Daiqing GAO
Chinese Journal of Hepatology 2015;23(9):658-662
OBJECTIVETo investigate the mechanisms underlying the ability ofheparin-treated dendritic cells (DCs) to promote Th0 to Th1 differentiation in chronic hepatitis B (CHB).
METHODSPeripheral blood mononuclear cells (PBMCs) were isolated from CHB patients and cultured in RPMI-1640 with recombinant GM-CSF and IL-4 with or without heparin to obtain DCs for study. The levels of Toll-like receptors (TLRs) on the DCs were measured using FACS and qPCR techniques.DC subsets with high expression of TLRs were selected for analysis of functional changes by treatment with the corresponding TLR-siRNA. The CD4+ T cell subpopulation was purified from peripheral blood by Dynal immunomagnetic beads, and then the production of IL-12 by DCs in the presence of poly(I:C) or R848 and ofIFN and IL-4 by Th cells co-cultured with DCs was evaluated by ELISA. The t-test was used for statistical analysis.
RESULTSTLR3 expression, and not expression of TLR 7 or TLR8,was significantly increased in heparin-treated DCs as compared to levels detected in the DCs without heparin treatment (t =2.849,P less than 0.05;t =3.027,P less than 0.05). The level of IL-12 produced by heparin-treated DCs stimulated with poly(I:C) was obviously higher than that produced by DCs without heparin treatment and stimulated with poly(I: C) (t =8.68,P less than 0.01) or with R848 (t =19.01,P less than 0.01). However, the IL-12 production by TLR3-siRNA transfected-DCs was significantly reduced (t =31.49, P less than 0.01).When Th cells from allogenic patients with CHB were co-cultured with the TLR3-siRNA transfectedDCs, the frequency ofCD4+ IFN+ cells was significantly reduced (1.64+/-0.57% vs.6.31+/-0.88%,P less than 0.01),as was the capability of Thl to generate IFNg (t =20.83,Pless than 0.01).
CONCLUSIONHeparin may have up-regulated the TLR3 expression level of DCs, and sequentially promoted Th0 to Th1 differentiation.
CD4-Positive T-Lymphocytes ; cytology ; Cell Differentiation ; Coculture Techniques ; Dendritic Cells ; cytology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Heparin ; pharmacology ; Hepatitis B, Chronic ; immunology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; pharmacology ; Monocytes ; cytology ; Recombinant Proteins ; pharmacology ; Toll-Like Receptor 3 ; metabolism
4.Effects of rhG-CSF Stimulation in vitro on the Adhesion and Polarization of Human CD4⁺T Lymphocytes.
Sha-Sha ZHAO ; Zhen-Yang GU ; Meng LI ; Xiao-Li ZHAO ; Lan LUO ; Li-Xun GUAN ; Li-Li WANG ; Chun-Ji GAO
Journal of Experimental Hematology 2014;22(6):1702-1706
The adhesion and polarization of T lymphocytes involved in the adhesive interaction of lymphocyte function-associated antigen 1 (LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulation in vitro on the adhesion and polarization of CD4⁺ T cells of healthy human in peripheral blood. The peripheral blood mononuclear cells were collected from 12 healthy volunteers. The CD4⁺ T cells were sorted by miniMACS. The sorted CD4⁺ T cells were incubated with rhG-CSF for 24 h, then the adhesion and polarization of CD4⁺ T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by ELISA and inverted microscope. The results showed that the percentage of adhesion CD4⁺T cells in the experimental group (rhG-CSF acting on the healthy adult volunteers) (61.9 ± 5.9)% was lower than that in the control group (healthy adult volunteers without rhG-CSF stimulation) (68.3 ± 7.3)% (P < 0.05). The percentage of polarized CD4⁺T cells in the experimental group (24.3 ± 4.3)% was also lower than that in control group (47.1 ± 5.1)% (P < 0.05). It is concluded that the adhesion and polarization of CD4⁺T lymphocytes can be inhibited after rhG-CSF stimulation.
Aged
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CD4-Positive T-Lymphocytes
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drug effects
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Cell Adhesion
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drug effects
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Cell Movement
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Cell Polarity
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drug effects
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Chemokine CXCL12
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Granulocyte Colony-Stimulating Factor
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pharmacology
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Humans
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In Vitro Techniques
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Intercellular Adhesion Molecule-1
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Leukocytes, Mononuclear
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Lymphocyte Activation
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Lymphocyte Function-Associated Antigen-1
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Middle Aged
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Recombinant Proteins
5.Effects of rhG-CSF mobilization on the polarization and migration of donor's CD4(+)T lymphocytes.
Zhen-Yang GU ; Meng LI ; Sha-Sha ZHAO ; Bo CAI ; Xiao-Li ZHAO ; Li-Xun GUAN ; Li-Li WANG ; Chun-Ji GAO
Journal of Experimental Hematology 2014;22(2):470-474
The polarization and migration of T lymphocytes involves the adhesive interaction of lymphocyte function-associated antigen 1(LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilization on the polarization and migration of donor's CD4(+) T cells in peripheral blood. The peripheral blood mononuclear cells were collected from 10 healthy volunteers and 10 donors on the fifth day of mobilization with rhG-CSF. And the CD4(+)T cells were purified by miniMACS. The polarization and migration of CD4(+) T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by using inverted and confocal microscopes respectively. The results showed that the percentage of polarized CD4(+)T cells from donors(32.42 ± 4.91)% was lower than that from healthy controls(56.55 ± 5.35)% (P < 0.01), the migration velocity of CD4(+)T cells from donors (7.06 ± 1.44 µm/min) was also lower than that of healthy controls(9.05 ± 1.91 µm/min)(P < 0.01). It is concluded that the polarization and migration of CD4(+)T lymphocytes is impaired after rhG-CSF mobilization.
Adolescent
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Adult
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CD4-Positive T-Lymphocytes
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cytology
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drug effects
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Case-Control Studies
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Cell Movement
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Female
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Granulocyte Colony-Stimulating Factor
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pharmacology
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Humans
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Male
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Middle Aged
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Recombinant Proteins
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pharmacology
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Tissue Donors
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Young Adult
6.Effect and mechanism of high-dose Vitamin B3 on granulopoiesis in normal rat.
Hu YANG ; Dan LAN ; Mengjie WANG ; Xinye LI ; Zongyan GAO ; Lindi LI
Chinese Journal of Hematology 2014;35(10):931-935
OBJECTIVETo investigate the effect and mechanism of high dose Vitamin B3 on granulopoiesis in normal rat.
METHODSTwenty one healthy SD rats were randomly divided into three groups: the Vitamin B3 group (Vit B3 500 mg·kg⁻¹·d⁻¹, × 7 d), the rhG-CSF group (rhG-CSF 25 μg·kg⁻¹·d⁻¹, × 7 d) and the normal saline group (2 ml/d, × 7 d). The peripheral blood cell counts were analyzed by automatic blood cell counter before (day 0) treatment, the third day (day 3) and the seventh day (day 7) after administration of drugs, respectively. The concentration of serum nicotinamide adenine dinucleotide (NAD⁺) level was measured by enzymatic cycling assay before and after drugs treatment. The expressions of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPβ, C/EBPε and NAMPT mRNA were detected by reverse transcription real-time fluorescent quantitative PCR.
RESULTSThe neutrophil counts increased significantly after 7 days of Vitamin B3 and rhG-CSF treatment compared with that of control group [(1.64 ± 0.19) × 10⁹/L, (1.88 ± 0.37)× 10⁹/L vs (0.86 ± 0.18) × 10⁹/L, P<0.01]; the level of serum NAD⁺ increased significantly [(0.96 ± 0.08) nmol/L, (0.65 ± 0.12) nmol/L vs (0.36 ± 0.15) nmol/L, P<0.01]; the expression of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPε and NAMPT mRNA in bone marrow mononuclear cells were increased significantly compared with that of control group (P<0.01).
CONCLUSIONHigh dose of Vitamin B3 may play an important role in increasing absolute neutrophil count in healthy rat under steady state, and the mechanism may be dependent on NAMPT-NAD⁺-SIRT1 signaling pathways.
Animals ; Bone Marrow Cells ; Granulocyte Colony-Stimulating Factor ; Leukocyte Count ; Neutrophils ; drug effects ; Niacinamide ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins
7.Effects of recombinant human granulocyte-macrophage colony-stimulating factor on wound healing and microRNA expression in diabetic rats.
Yifeng LIU ; Dewu LIU ; Guanghua GUO ; Yuangui MAO ; Xianlin WANG
Chinese Journal of Burns 2014;30(3):243-250
OBJECTIVETo investigate the effects of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) on wound healing and microRNA expression in diabetic rats.
METHODSEighteen male SD rats of clean grade were used to reproduce diabetes model. Four weeks later, a total of 64 full-thickness skin wounds were created on the back of 16 rats with established diabetes, with 4 wounds on each rat. Two symmetrical wounds on either side of the spine were created as a pair according to paired design. Then the wounds were divided into groups A and B according to the random number table and blind method (red and blue tags on the rhGM-CSF or the gel vehicle), with 32 wounds in each group. The ointment with red tag was applied on the wounds of group A and the blue one on group B. The application was conducted once a day, with a thickness of 3 mm, up to post injury day (PID) 14. Gross observation of wound healing was conducted on PID 3, 7, 14. The wound healing rate was determined on PID 3 and 7. On PID 3, 7, 14, tissues from 2, 4, and 8 wounds were harvested from each group respectively for the observation of the histopathological changes with HE staining, and also for analyzing the expression of proliferating cell nuclear antigen (PCNA) and CD31 with immunohistochemical staining (denoted as absorbance value). On PID 7, tissues from 6 wounds in each group were harvested for microarray gene chip to screen the differentially expressed microRNAs. Enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway on the differentially expressed microRNAs were performed after the microRNA screening results were validated by real-time fluorescent quantitative RT-PCR. Data were processed with paired t test or two-sample t test.
RESULTS(1) On PID 3, the wound area was significantly decreased, and the wound granulation was significantly proliferated in both groups. On PID 7, the wound area was further decreased, and the wound area was almost filled by granulation in both groups; the conditions in group A were better. On PID 14, all the wounds in group A were almost healed, while a small area of raw wound with incrustation still remained in some wounds of group B. On PID 3 and 7, the wound healing rates of group A were (41 ± 5)% and (75 ± 4)%, significantly higher than those of group B [(31 ± 9)% and (71 ± 4)%, with t values respectively 10.13 and 8.06, P values below 0.001]. (2) On PID 3, the epidermal cells, endothelial cells, and Fbs in the wounds of 2 groups were sparse, with heavy infiltration of inflammatory cells. The above condition in the wounds was better in group A than in group B. On PID 7, the epidermal cells, endothelial cells, and Fbs were gradually well arranged in group A; infiltration of inflammatory cells decreased, and the condition was better than that of group B. On PID 14, the wounds of group A were completely covered by epidermis, while infiltration of inflammatory cells still remained in some wounds of group B. (3) On PID 3, 7, 14, the positive expressions of CD31 and PCNA in group A were respectively 0.275 ± 0.018, 0.345 ± 0.034, 0.305 ± 0.023; 0.406 ± 0.063, 0.223 ± 0.011, 0.045 ± 0.022. They were significantly higher than those of group B (0.222 ± 0.020, 0.229 ± 0.018, 0.197 ± 0.015; 0.324 ± 0.039, 0.162 ± 0.012, 0.018 ± 0.020, with t values from 2.281 to 9.652, P < 0.05 or P < 0.01). (4) According to the microRNAs detection and screening, as compared with group B, 18 microRNAs were up-regulated while 13 were down-regulated in the wounds of group A. (5) The results of real-time fluorescent quantitative RT-PCR had good consistency with the results of microRNAs detection. (6) Enrichment analysis of KEGG signaling pathway showed that among the 31 differentially expressed microRNAs, 4 took part in the MAPK signaling pathway, 3 took part in the Wnt signaling pathway, 1 took part in the TGF-β signaling pathway, 3 took part in the epidermal growth factor receptor signaling pathway, 2 took part in the cell cycle pathway, 5 took part in the axon guidance signaling pathway, 6 took part in the focal adhesion pathway, 3 took part in the regulation of actin cytoskeleton pathway, 1 took part in the extracellular cell matrix receptor pathway, 3 took part in the adherens junction pathway, and 1 took part in the cell adhesion molecules pathway. After disclosing the blind, it showed that the ointment with red tag was the rhGM-CSF gel and the blue one was gel vehicle.
CONCLUSIONSThe rhGM-CSF gel can promote wound healing in diabetic rats, producing significant differential microRNA expression in wounds, and they may be the target at gene post-transcriptional level of rhGM-CSF gel in promoting wound healing.
Animals ; Bacteria ; isolation & purification ; Burns ; drug therapy ; microbiology ; pathology ; Diabetes Mellitus, Experimental ; complications ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Male ; MicroRNAs ; genetics ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Recombinant Proteins ; Signal Transduction ; Wound Healing ; drug effects
8.Effect of granulocyte-macrophage colony-stimulating factor on the mammalian target of sirolimus signaling pathway in the wound of rat.
Wen-hui CUI ; Hong HUANG ; Xiang XU ; Min GUO ; Hui DAI ; Yu JIAN ; Wei GUO ; Wei XING ; Jian-xin JIANG ; Rong YANG
Chinese Journal of Burns 2012;28(1):36-41
OBJECTIVETo investigate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on wound healing and mammalian target of sirolimus (rapamycin) signaling pathway in rats.
METHODSFifty SD rats were divided into control group (n = 25) and treatment group (n = 25) according to the random number table. All rats were inflicted with 2 cm × 2 cm full-thickness skin wound on the back. Recombinant human GM-CSF gel (10 µg/cm(2)) was applied onto the wounds in treatment group, and the actual quantity was 1 × 10(-4) µg/cm(2). Gel vehicle (10 µg/cm(2)) without any medicine was applied onto the wounds in control group. The treatment was conducted once a day up to the day of wound healing. Five rats from two groups were sacrificed on post injury day (PID) 1, 3, 5, 7, 14 respectively to observe and determine the wound healing rate. Wound tissue samples were collected at the former 4 time points to observe the histopathological changes with HE staining, and to detect the content of GM-CSF with enzyme-linked immunosorbent assay, and the expression levels of GM-CSF, CD31, and the mTOR signal pathway associated molecules P70S6K, phosphorylated (p-) P70S6K, 4E-BP1, p-4E-BP1, mTOR, p-mTOR with Western blotting. Data were processed with t test.
RESULTS(1) Wound healing rates in control group and treatment group were close on PID 1 (t = 0.307, P > 0.05). Wound healing rate in treatment group was obviously higher than that in control group on PID 3, 5, 7, and 14 (with t values from 2.704 to 4.030, P < 0.05 or P < 0.01). (2) Compared with those in control group, more abundant granulation tissue was observed in treatment group, in which an increase in the number of microvessels and obvious proliferation of keratinized epithelial cells in wound margin were observed at each time point. (3) The content and the protein expression level of GM-CSF peaked on PID 3 in two groups, and they were (720.9 ± 0.9) pg/mL, 2.45 ± 0.10 in control group and (910.5 ± 1.3) pg/mL, 2.80 ± 0.48 in treatment group. The content of GM-CSF in treatment group was significantly higher than that in control group at each time point (with t values from 105.743 to 298.971, P values all equal to 0.000). The protein expression level of GM-CSF in treatment group was significantly higher than that in control group on PID 1, 5, and 7 (with t values from 4.070 to 5.275, P values all below 0.01). (4) The expression level of CD31 in treatment group was obviously higher than that in control group on PID 1, 3, and 7 (with t values from 7.237 to 26.401, P values all below 0.01). (5) The expression levels of mTOR and p-mTOR in treatment group were significantly higher than those in control group at each time point (with t values from 2.921 to 23.143, P < 0.05 or P < 0.01). In treatment group, the expression level of P70S6K was obviously higher than that in control group on PID 3, 5, and 7 (with t values from 2.950 to 5.275, P < 0.05 or P < 0.01), and the expression level of p-P70S6K was significantly higher than that in control group on PID 1, 3, and 7 (with t values from 3.307 to 22.793, P < 0.05 or P < 0.01). In treatment group, the expression level of 4E-BP1 was significantly lower than that in control group on PID 1, 3, and 5 (with t values from 2.449 to 6.431, P < 0.05 or P < 0.01), but the expression level of p-4E-BP1 was significantly higher than that in control group on PID 1, 3, and 7 (with t values from 5.522 to 11.613, P values all below 0.01).
CONCLUSIONSGM-CSF can promote wound healing in rats by activating mTOR signaling pathway through phosphorylating mTOR proteins and its downstream signal molecules P70S6K and 4E-BP1.
Animals ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology ; Signal Transduction ; drug effects ; Sirolimus ; pharmacology ; TOR Serine-Threonine Kinases ; metabolism ; Wound Healing ; drug effects
9.Mobilization and collection of autologous peripheral blood stem cells by CIE or IEV protocol in children with malignant solid tumors.
Yi ZHANG ; Wei-Ling ZHANG ; Dong-Sheng HUANG ; Yi-Ping YANG ; Xiao-Chao LIU ; Yi-Ping WU
Chinese Journal of Contemporary Pediatrics 2011;13(6):471-474
OBJECTIVEAutologous peripheral blood stem cell transplantation (APBSCT) is an important method for treatment of malignant solid tumors in children. The mobilization and collection of blood stem cells is crucial for APBSCT. This study aimed to evaluate the clinical efficacy of mobilization and collection of blood stem cells by CIE or IEV chemotherapy protocol in APBSCT in children with neuroblastoma (NB) or rhabdomyosarcoma.
METHODSThe protocols of CIE (cisplatin, etoposide) and IEV (vincristine, dosfamide, etoposide) were used as mobilization chemotherapy in 8 cases of NB with stage IV and 3 cases of rhabdomysacoma with stage III, respectively. The results of the mobilization of blood stem cells were observed.
RESULTSOf the 11 cases, mononuclear cells (MNC) and CD34+ cells were successfully collected and the volume of MNC and CD34 averaged (5.55 ± 1.43)× 10(8)/kg and (4.88 ± 2.48) × 10(6)/kg, respectively. No severe complications were observed during the mobilization and collection. A rapid hemopoietic reconstitution was observed in 10 children after APBSCT. One with NB out of the 10 children died of left heart failure 32 days after APBSCT. Others (9 cases) showed a nearly normal result of routine peripheral blood test 60 days after APBSCT.
CONCLUSIONSCIE or IEV protocol is effective and safe for the mobilization and collection of peripheral blood stem cells in children with NB or rhabdomysacoma.
Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; pharmacology ; Child ; Child, Preschool ; Epirubicin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; adverse effects ; methods ; Humans ; Ifosfamide ; administration & dosage ; Male ; Neuroblastoma ; therapy ; Peripheral Blood Stem Cell Transplantation ; Recombinant Proteins ; Rhabdomyosarcoma ; therapy ; Transplantation, Autologous
10.A comparison of NK cell subsets between rhG-CSF mobilized peripheral blood grafts and bone marrow grafts from healthy donors.
Ling-ling XU ; Xiao-jun HUANG ; Xiang-yu ZHAO
Chinese Journal of Hematology 2011;32(2):79-82
OBJECTIVETo analyze the difference in NK cell subsets between recombination human granulocyte colony-stimulating factor (rhG-CSF) mobilized peripheral blood grafts (G-PB) and bone marrow grafts (G-BM) from healthy donors.
METHODSFrom July 2009 to September 2009, G-PB and G-BM from 28 related donors were collected to analyze lymphocytes, NK cells and NK cell secretion of interferon-γ (IFN-γ, NK1), interleukin-13 (IL-13, NK2), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10, NKr) by flow cytometry.
RESULTSThe percentage of lymphocytes in G-PB was significantly higher than that in G-BM (P < 0.01). The proportions of NK cells and NK1, NK2, NKr subsets among lymphocytes were significantly higher in G-BM than in G-PB (P < 0.05), and so were the percentage of NK2, NKr cells among NK cells (P < 0.01), but no significant difference in the percentage of NK1 cells among NK cells between G-PB and G-BM. The ratios of IL-13 and IFN-γ, of TGF-β and IFN-γ, or of IL-10 and IFN-γ in G-BM were significantly higher than those in G-PB (P = 0.010, 0.002, or 0.000, respectively).
CONCLUSIONThe increased proportion of NK2 and NKr in G-BM might be helpful to explain the lower immunoreactivity of G-BM than that of G-PB, although the proportion of NK1 in G-BM and G-PB is similar.
Adolescent ; Adult ; Blood Donors ; Bone Marrow Cells ; cytology ; Child ; Cytokines ; secretion ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Killer Cells, Natural ; cytology ; secretion ; Male ; Middle Aged ; Recombinant Proteins ; pharmacology ; Young Adult

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