1.Pro- and anti-inflammatory cytokine expression and histopathological characteristics in canine brain with traumatic brain injury.
Chi Ho YU ; Ji Young YHEE ; Jong Hyuk KIM ; Keum Soon IM ; Na Hyun KIM ; Dong In JUNG ; Hee Chun LEE ; Seung Ki CHON ; Jung Hyang SUR
Journal of Veterinary Science 2011;12(3):299-301
We analyzed the expression level and cellular localization of pro- and anti-inflammatory cytokines and histopathologically characterized canine traumatic brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and vasogenic edema. Immunohistochemical evaluations suggested that both pro-inflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta (TGF-beta)] were highly expressed in neurons and neutrophils. In particular, the highest magnitude of expression was identified for IL-1beta and TGF-beta. This data helps describe the pathologic characteristics of canine TBI, and may help in the design of potential therapeutic approaches to control secondary damage by inflammatory cytokines.
Animals
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Brain/*immunology/*pathology
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Brain Injuries/immunology/*pathology/*veterinary
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Dogs
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Humans
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Interleukin-10/immunology/metabolism
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Interleukin-1beta/immunology/metabolism
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Interleukin-6/immunology/metabolism
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Transforming Growth Factor beta/immunology/metabolism
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Tumor Necrosis Factor-alpha/immunology/metabolism
2.Porphyromonas gingivalis vesicle induced cellular inflammatory responses of gingival epithelial cells in vitro.
Chinese Journal of Stomatology 2007;42(9):564-567
OBJECTIVETo establish the model of cellular inflammatory responses of gingival epithelial cells in vitro induced by Porphyromonas gingivalis vesicle and to probe into the pathogenesis of Porphyromonas gingivalis in periodontitis.
METHODSThe effect of Porphyromonas gingivalis vesicle on prostaglandin E(2) (PGE(2)) production of gingival epithelial cells was detected by ELISA and the effects of Porphyromonas gingivalis vesicle on cyclooxygenase-2 (COX-2), interleukin (IL)-6 and IL-8 mRNA expression in gingival epithelial cells were determined by Real-time reverse transcription-polymerase chain reaction (RT-PCR).
RESULTSPorphyromonas gingivalis vesicle dose-dependently induced PGE(2) production and up-regulated COX-2, IL-6 and IL-8 mRNA expression in gingival epithelial cells significantly.
CONCLUSIONSCellular inflammatory responses of gingival epithelial cells induced by Porphyromonas gingivalis vesicle may contribute to the initiation and progression of periodontitis.
Bacterial Adhesion ; Cells, Cultured ; Cyclooxygenase 2 ; immunology ; metabolism ; Dinoprostone ; immunology ; metabolism ; Epithelial Cells ; immunology ; metabolism ; microbiology ; Gingiva ; immunology ; metabolism ; microbiology ; Humans ; Interleukin-6 ; immunology ; metabolism ; Interleukin-8 ; immunology ; metabolism ; Porphyromonas gingivalis ; immunology ; pathogenicity
3.Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients.
Li-Fei SUN ; Bing HAN ; Qiang-Qiang WU ; Xiao-Xi ZHANG ; Yan-Hui DU ; Gui-Chen WANG ; Jin-Biao ZHANG ; Yan ZHANG
Chinese Medical Journal 2013;126(24):4696-4702
BACKGROUNDImmune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage (Mφ) in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Mφ in hematopoietic cell injury.
METHODSELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-γ levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase (POX), nonspecific esterase (NSE), hemosiderin granules, and HLA-DR activity of Mφ in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Mφ membrane FcγIIreceptor (FcγIIR), mannitose receptor (MR), IFN-γ, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) hematopoietic cell islands (HI) in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Mφ bloodthirsty phenomenon; if necessary, association of Cyclosporine A (CsA) should be used and chalybeate should be supplemented.
RESULTSIn the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-γ were increased. After treatment, the cytokine levels gradually became normal. The activated Mφ in the marrow highly expressed NSE and POX, and Mφ swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Mφ expressed HLA-DR, MR, ICAM-1, IFN-γ, and IL-12. For patients with humoral immunity activation and bacterial infection, Mφ weakly expressed IL-17A but highly expressed FcγIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count (WBC) significantly reduced, Mφ weakly expressed FcγIIR, secretory highly expressed IL-17A, and the phenomena that Mφ adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Mφ occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve.
CONCLUSIONSMφ is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Mφ, upregulate the impression of immune molecule and receptors, form ADCC HI, aggravate hematopoietic injury, and accelerate the destruction on hematopoietic cell.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-17 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-6 ; metabolism ; Macrophages ; immunology ; metabolism ; Male ; Middle Aged ; Pancytopenia ; immunology ; metabolism ; Young Adult
4.Hepatitis B e antigen perturbs the LPS-stimulated production of inflammatory cytokines by mononuclear-derived dendritic cells.
Yong-zhi TANG ; Fei YAN ; Ke-chuan PAN ; Jian-sheng ZHU ; Hua-zhong CHEN ; Min ZHU ; Xi LIN ; Hai-hong ZHAO ; Ming XIAO
Chinese Journal of Hepatology 2013;21(8):590-593
OBJECTIVETo investigate whether hepatitis B e antigen (HBeAg) can modulate the ability of dendritic cells (DCs) to produce inflammatory cytokines (IL-12/IL-6) upon stimulation in vitro.
METHODSPurified adherent mononuclear cells isolated by Ficoll-hypaque density gradient centrifugation were cultured in complete medium containing granulocyte macrophage colony-stimulating factor plus interleukin (IL)-4 to generate immature (i)DCs. Microscopic analysis and flow cytometry were performed to define the phenotypic characteristics of the iDCs. Then, different concentrations (1, 2 and 5 mug/ml) of HBeAg were added to the culture medium and for 24 hrs of incubation. To induce iDCs' maturation, the various groups of cells were incubated for 24 hrs in differentiation culture with lipopolysaccharide (LPS). Effects on secreted inflammatory cytokines were determined by enzyme-linked immunosorbent assay of the cells' supernatants.
RESULTSAll concentrations of HBeAg led to significant reductions in IL-6 (all P less than 0.05). Similar significant reduction trends were seen for IL-12 at the HBeAg concentrations of 2 and 5 mug/ml (both P less than 0.05), but not at the 1 mug/ml concentration.
CONCLUSIONHBeAg may suppress the production of cytokines from DCs; this mechanism may contribute to the immune escape of HBV that supports persistent infection.
Cells, Cultured ; Dendritic Cells ; immunology ; metabolism ; Hepatitis B e Antigens ; immunology ; Humans ; Interleukin-12 ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; adverse effects
5. Modulates Vaginal Epithelial Cell Innate Response to.
Xiao-Xi NIU ; Ting LI ; Xu ZHANG ; Su-Xia WANG ; Zhao-Hui LIU
Chinese Medical Journal 2017;130(3):273-279
BACKGROUNDVulvovaginal candidiasis is caused by Candida albicans. The vaginal epithelium, as the first site of the initial stage of infection by pathogens, plays an important role in resisting genital tract infections. Moreover, lactobacilli are predominant members of the vaginal microbiota that help to maintain a normal vaginal microenvironment. Therefore, Lactobacillus crispatus was explored for its capacity to intervene in the immune response of vaginal epithelial cells VK2/E6E7 to C. albicans.
METHODSWe examined the interleukin-2 (IL-2), 4, 6, 8, and 17 produced by VK2/E6E7 cells infected with C. albicans and treated with L. crispatus in vitro. The capacity of L. crispatus to adhere to VK2/E6E7 and inhibit C. albicans growth was also tested by scanning electron microscopy (SEM) and adhesion experiments.
RESULTSCompared with group VK2/E6E7 with C. albicans, when treated with L. crispatus, the adhesion of C. albicans to VK2/E6E7 cells decreased significantly by 52.87 ± 1.22%, 47.03 ± 1.35%, and 42.20 ± 1.55% under competition, exclusion, and displacement conditions, respectively. SEM revealed that the invasion of C. albicans into VK2/E6E7 cells was caused by induced endocytosis and active penetration. L. crispatus could effectively protect the cells from the virulence of hyphae and spores of C. albicans and enhance the local immune function of the VK2/E6E7 cells. The concentrations of IL-2, 6, and 17 were upregulated significantly (P < 0.01) and that of IL-8 were downregulated significantly (P < 0.01) in infected VK2/E6E7 cells treated with L. crispatus. The concentration of IL-4 was similar to that of the group VK2/E6E7 with C. albicans (24.10 ± 0.97 vs. 23.12 ± 0.76 pg/ml, P = 0.221).
CONCLUSIONSL. crispatus can attenuate the virulence of C. albicans, modulate the secretion of cytokines and chemokines, and enhance the immune response of VK2/E6E7 cells in vitro. The vaginal mucosa has a potential function in the local immune responses against pathogens that can be promoted by L. crispatus.
Candida albicans ; pathogenicity ; Cell Line, Tumor ; Epithelial Cells ; immunology ; metabolism ; microbiology ; ultrastructure ; Female ; Humans ; Interleukin-17 ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Lactobacillus crispatus ; physiology ; Microscopy, Electron, Scanning ; Vagina ; cytology
6.Role of glutamine in the mediation of E-cadherin, p120-catenin and inflammation in ventilator-induced lung injury.
Jian-Lei QIU ; ; Bai-Ling SONG ; Yu-Juan WANG ; Fu-Tao ZHANG ; Yue-Lan WANG
Chinese Medical Journal 2018;131(7):804-812
BackgroundVentilator-induced lung injury (VILI) is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated. This study examined the relationship between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were ameliorated by glutamine in VILI, both in vitro and in vivo.
MethodsFor the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table (n = 6 in each group): control (Group C); low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence.
ResultsIn vivo, compared with Group C, total cell counts (t = -28.182, P < 0.01), the percentage of neutrophils (t = -28.095, P < 0.01), IL-6 (t = -28.296, P < 0.01), and TNF-α (t = -19.812, P < 0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = -6.708, P < 0.01), and the wet-to-dry ratio (t = -15.595, P < 0.01) were increased in Group H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t = 10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01), and TNF-α (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G; IL-10 in BAL fluid (t = -7.531, P < 0.01) and the expression of E-cadherin (t = -14.814, P < 0.01) and p120-catenin (t = -9.114, P < 0.01) were increased in Group H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = -21.111, P < 0.01) and TNF-α (t = -15.270, P < 0.01) were increased in the 20% cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P < 0.01) were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-α (t = 8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = -3.203, P < 0.05) and the expression of E-cadherin (t = -13.567, P < 0.01) and p120-catenin (t = -10.013, P < 0.01) were increased in the glutamine group.
ConclusionsHigh tidal volume mechanical ventilation and 20% cyclic stretching could cause VILI. Glutamine regulates VILI by improving cytokines and increasing the adherens junctions, protein E-cadherin and p120-catenin, to enhance the epithelial barrier function.
Animals ; Cadherins ; metabolism ; Catenins ; metabolism ; Glutamine ; metabolism ; Inflammation ; metabolism ; Interleukin-6 ; metabolism ; Lung ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Ventilator-Induced Lung Injury ; immunology ; metabolism
7.Effects of intestinal trefoil factor combined with mucin on immune function of burn serum treated intestinal epithelial cells.
Xiu-Wen WU ; Huan WANG ; Qian-Xue WAN ; Xing JIN ; Yong SUN ; Dan WU ; Jun-Jie CAO ; Xi PENG
Chinese Journal of Burns 2011;27(5):341-346
OBJECTIVETo observe the effect of intestinal trefoil factor (ITF) combined with mucin on immune function of intestinal epithelial cells (IEC) after being treated with burn rat serum.
METHODSThe rat IEC-6 cell lines were divided into control group (C, cultured in DEME medium containing 10% calf serum), burn control group (BC, cultured in DEME medium containing 10% burn rat serum), burn serum + ITF group (B + I, cultured in DEME medium containing 10% burn rat serum and 25 microg/mL ITF), burn serum + mucin group (B + M, cultured in DEME medium containing 10% burn rat serum and 250 microg/mL mucin), and burn serum + ITF + mucin group (B + I + M, cultured in DEME medium containing 10% burn rat serum, 25 microg/mL ITF, and 250 microg/mL mucin) according to the random number table. Meanwhile, 200 microL suspension of E. coli with density of 1 x 10(8) CFU/mL was added to each culture. At post culture minute (PCM) 15, 30 and post culture hour (PCH) 1, 2, 3, the number of bacteria adherent to IEC-6 was counted after Wright-Giemsa staining, and cell survival rate was calculated after trypan blue staining, with 20 samples in each group at each time point. (2) Other samples of IEC-6 cells without addition of E. coli were divided into BC, B + I, B + M, and B + I + M groups with the same treatment as above. The supernatant contents of IL-6, IL-8, and TNF-alpha were determined by radioimmunoassay at PCH 3, 6, 12, 24, 48, with 6 samples in each group at each time point. Data were processed with t test.
RESULTS(1) Compared with that in C group, count of adherent bacteria to IEC-6 in BC group at each time point was significantly increased (with t values from 2.947 to 8.149, P values all below 0.01). Compared with those in BC group, the counts in B + I, B + M, B + I + M groups at the major time points were significantly decreased (with t values from -4.733 to -2.180, P < 0.05 or P < 0.01). (2) Compared with that in C group, cell survival rate in BC group at each time point was obviously lowered (with t values from -4.126 to -2.363, P values all below 0.05). Cell survival rates in B + I and B + M groups at some time points were significantly elevated as compared with those in BC group (with t values from 2.120 to 3.423, P < 0.05 or P < 0.01). Cell survival rate in B + I + M group at PCM 15 and PCH 3 was respectively (96.7 +/- 2.4)% and (84.0 +/- 6.7)%, which was respectively higher than that in B + I and B + M groups [(94.5 +/- 3.1)%, t = 2.507, P < 0.05; (77.1 +/- 8.2)%, t = 2.934, P < 0.01]. (3) The contents of TNF-alpha in supernatant of B + I + M group at PCH 6, 12, 24, 48 were significantly lower than those in the other 3 groups (with t values from -6. 914 to -2.889, P < 0.05 or P < 0.01). The contents of IL-6 in supernatant of B + I + M group at some time points were significantly lower than those in the other 3 groups (with t values from -7. 657 to -2.580, P < 0.05 or P < 0.01). The contents of IL-8 in supernatant of B + I + M group at PCH 6, 12, 24, 48 were significantly lower than those in BC and B + M groups (with t values from - 8.802 to - 3.640, P values all below 0.01), and those in B + I + M group at PCH 12, 24 were lower than those in B + I group (with t value respectively -2.786, -2.740, P value all below 0.05).
CONCLUSIONSITF can maintain immune function and homeostasis of IEC, prevent bacterial adherence, decrease cell death rate, and reduce release of inflammatory mediators. The effect can be strengthened with addition of mucin.
Animals ; Bacterial Adhesion ; Burns ; blood ; Cell Line ; Epithelial Cells ; drug effects ; immunology ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Intestines ; cytology ; immunology ; metabolism ; Mucins ; pharmacology ; Peptides ; pharmacology ; Rats ; Serum ; immunology ; Trefoil Factor-2 ; Tumor Necrosis Factor-alpha ; metabolism
8.Ischemic preconditioning produces more powerful anti-inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury.
Jia-qiang ZHANG ; Qiang WANG ; Fu-shan XUE ; Rui-ping LI ; Yi CHENG ; Xin-long CUI ; Xu LIAO ; Fan-min MENG
Chinese Medical Journal 2013;126(20):3949-3955
BACKGROUNDBoth ischemic preconditioning (IPC) and limb remote ischemic postconditioning (LRIPOC) have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury (IRI), but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.
METHODSEighty rats were randomly allocated into four equal groups: sham group, IRI group, IPC group and LRIPOC group. In 10 rats randomly selected from each group, serum levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 were assessed, and infarct size was determined. In another 10 rats of each group, myocardial levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 in both ischemic and non-ischemic regions were measured.
RESULTSThe infarct size was significantly lower in IPC and LRIPOC groups than in IRI group. The serum and myocardial levels of pro-inflammatory cytokines including TNF-α, HMGB1, ICAM1, IL-1 and IL-6 during reperfusion were significantly reduced in IPC and LRIPOC groups compared to IRI group. As compared to the IPC group, infarct size, serum level of TNF-α at 60 minutes of reperfusion, serum levels of HMGB1 and ICAM1 at 120 minutes of reperfusion, myocardial levels of TNF-α, ICAM1, IL-1 and IL-6 in the ischemic region, myocardial levels of ICAM1, IL-1 and IL-6 in the non-ischemic region were significantly increased in the LRIPOC group.
CONCLUSIONSIn the rats with myocardial IRI, IPC produces more powerful inhibitory effects on local myocardial and systemic inflammatory responses than LRIPOC. This may be partly attributed to more potent cardioprotection produced by IPC.
Animals ; HMGB1 Protein ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-1 ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-6 ; metabolism ; Ischemic Postconditioning ; methods ; Ischemic Preconditioning ; methods ; Male ; Myocardial Reperfusion Injury ; immunology ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism
9.Expression and significance of interleukin-6, interferon-inducible protein-10 and interleukin-17 in serum and synovial fluid of patients with juvenile idiopathic arthritis.
Rui-juan LI ; ; Xue-mei TANG ; Wei LIU ; Juan ZHOU ; Yun-fei AN ; Shi-ying QIN ; Zong-yi ZOU
Chinese Journal of Pediatrics 2013;51(6):472-476
OBJECTIVETo detect the disparity of three cytokines interleukin-6 (IL-6), interferon-inducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).
METHODSerum concentrations of the three cytokines were measured in 27 patients with 13 systemic-onset JIA (sJIA), 14 polyarticular JIA (pJIA) and 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Nineteen patients with no marked arthritis symptom or only temporary arthralgia were enrolled in probable sJIA group. SF from 18 patients with 7 sJIA, 11 pJIA were examined for cytokine levels.
RESULT(1) The statistically significant difference in serum IL-6 was detected between sJIA and healthy control group [28.0(4.2-59.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P < 0.05], but no significant difference between probable sJIA and healthy control group [11.8(7.7-39.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P > 0.05] was found. There were statistically significant differences between sJIA group and healthy control group in serum concentrations of IL-17 [14.0(9.8-34.3) ng/L vs. 9.8 (7.9-16.2) ng/L, P < 0.05], yet compared to healthy control group, no significant difference in concentration level of IL-17 was found in pJIA Group [14.2(9.9-16.9) ng/L vs. 9.8(7.9-16.2) ng/L, P > 0.05].(2) In sJIA and pJIA SF, the median IP-10 level was significantly higher compared to respective PB levels [619.7 (160.9, 873.1) ng/L vs. 64.8 (27.4-111.9) ng/L;660.9 (401.9, 1349.8) ng/L vs. 97.4 (41.9-222.1) ng/L, P < 0.01, respectively], but there was only significant difference in IL-17 between pJIA SF and PB [22.9 (17.1, 45.8) ng/L vs. 14.2 (9.9-16.9) ng/L, P < 0.01].
CONCLUSIONIL-6 may play more important role in the pathogenesis of sJIA. Moreover, IL-6 may be the biomarker associated with arthritis in early JIA stage. Both autoinflammation and autoimmune response may be involved in the pathogenesis of sJIA. IL-17 enrichment may only occur in local joint, the levels of IL-17 in PB may not be significantly increased. The prominent expression gradient between SF and PB of IP-10 maybe the basis of performing chemotaxis and further causing joint damage.
Adolescent ; Arthritis, Juvenile ; blood ; immunology ; metabolism ; Case-Control Studies ; Chemokine CXCL10 ; blood ; metabolism ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-17 ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Knee Joint ; metabolism ; Male ; Synovial Fluid ; immunology ; metabolism
10.Immunomodulatory effects of mesenchymal stem cells derived from the bone marrow in acute leukemia patients.
Zhi-gang ZHAO ; Li SUN ; Xiao-fang WANG ; Yi-zhuo ZHANG ; Yong YU ; Hong-liang YANG ; Ping ZOU
Chinese Journal of Oncology 2011;33(2):105-109
OBJECTIVETo study the immunomodulatory effects and mechanisms of mesenchymal stem cells (MSC) derived from the bone marrow in acute leukemia patients in vitro.
METHODSBone marrow mononuclear cells from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) were obtained and cultured in low serum medium. The immunophenotypes were assessed by FACS and immunol histochemistry. The levels of cytokines were evaluated by enzyme linked immunosorbant assay (ELISA). T-cell suppression ability was evaluated by Transwell chamber assay. Moreover, the immunoregulatory ability of AML- and ALL-derived MSC was detected by mixed lymphocyte culture assay.
RESULTSALL-derived MSC showed a typical fibroblast-like morphology. They were positive for CD29, CD44 and CD105, the positive rate were 98.81%, 99.25% and 90.52%, respectively, while negative for CD31, CD45 and CD34. Moreover, ALL- and AML-derived MSC didn't express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). ALL and AML derived MSC could secret several cytokines, such as TGF-β1 (567.58 ± 52.64 and 357.15 ± 33.52), HGF (647.27 ± 102.54 and 219.67 ± 62.37), IL-6 (59.67 ± 15.69 and 54.35 ± 12.31) and IL-11 (102.58 ± 23.54 and 78.21 ± 9.67), the level of secretion of TGF-β1 and HGF were higher in ALL bone marrow derived MSC than that of in AML bone marrow derived MSC. ALL and AML derived MSC significantly suppressed T lymphocyte proliferation in a dose-dependent manner, the counts per minute (CPM) were (3.58 ± 0.54) × 10(4), (2.87 ± 0.33) × 10(4), (1.78 ± 0.51) × 10(4) and (1.15 ± 0.15) × 10(4) for AML derived MSC, and CPM were (1.96 ± 0.31) × 10(4), (1.57 ± 0.28) × 10(4), (0.91 ± 0.41) × 10(4) and (0.22 ± 0.11) × 10(4) for ALL derived MSC when MSC were 0.5 × 10(4), 1 × 10(4), 2 × 10(4) and 5 × 10(4). In addition, the CPM was (4.01 ± 0.72) × 10(4) in control group. The immunosuppressive ability was different between MSCs derived from AML and ALL. The immunosuppressive effect of ALL derived MSC could be reversed by anti-TGF-β1 and anti-HGF antibody.
CONCLUSIONALL-derived MSC show immunoregulatory effect in vitro and this effect is achieved through cytokines. But MSCs derived from AML display abnormal changes in T-cell suppression ability.
Bone Marrow ; immunology ; Bone Marrow Cells ; cytology ; Cell Proliferation ; drug effects ; Cytokines ; pharmacology ; Humans ; Immunophenotyping ; Interleukin-11 ; metabolism ; Interleukin-6 ; metabolism ; Leukemia, Myeloid, Acute ; immunology ; Mesenchymal Stromal Cells ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; Transforming Growth Factor beta1 ; metabolism