Induced Proliferation (induced + proliferation)

Distribution by Scientific Domains

Selected Abstracts

Structural Evolution and Copper-Ion Release Behavior of Cu-pHEMA Hybrids Synthesized In Situ,

Yen-Yu Liu
Abstract A novel Cu-pHEMA hybrid was successfully prepared by in situ photopolymerization of 2-hydroxyethyl methacrylate (HEMA) monomer in the presence of Cu(II) copper ions, following an in situ chemical reduction. Experimental observations indicate that intermolecular interactions such as the coupling force and hydrogen bonding between the Cu and the hydroxyl groups further stabilize the hybrid structure to a considerable extent. Localization of the metallic copper particles within the pHEMA network structure as a result of those intermolecular interactions gives rise to the formation of discretely distributed nanocrystallites with particle sizes ranging from 5 to 25,nm in diameter. A crystallographic change of the Cu nanophase from an amorphous-like to a crystalline structure is observed as the H2O:HEMA molar ratio increases, upon synthesis, accompanied with an increase in the particle size. A relatively slow and sustained release of the Cu (in the form of cupric ions) from the hybrids was measured for a time period of about 10 days, which also illustrates a Cu(II)-induced proliferation of the endothelial cells over a relatively small range of release rate of the Cu from the hybrids. Such a new type of Cu-loaded hybrid hydrogel is expected to be compatible and may be considered as a candidate biomaterial for biomedical/therapeutic uses. [source]

Interleukin-6-induced proliferation of pre-B cells mediated by receptor complexes lacking the SHP2/SOCS3 recruitment sites revisited

FEBS JOURNAL, Issue 24 2001
Kerstin Friederichs
Interleukin-6 (IL-6) induces B-cell proliferation by binding to receptor complexes composed of a specific ,-receptor (gp80; CD126) and the signal transducing receptor subunit gp130 (CD130). Immediately after receptor complex activation, signal transducers and activators of transcription (STATs) 1 and 3 and the Src-homology domain-containing protein tyrosine phosphatase 2 (SHP2) are recruited to gp130 and subsequently tyrosine phosphorylated. The activated dimerized STATs translocate to the nucleus and bind to enhancer elements of IL-6-inducible genes. SHP2 acts as an adapter and links the Jak/STAT pathway to the Ras/Raf/MAPK cascade but it is also involved in signal attenuation. Whereas STAT3 activation appears to be crucial for all biological activities of IL-6, the requirement of SHP2-activation depends on the individual biological response analyzed. The requirement of SHP2 activation for the pre-B cell (Ba/F3) proliferation has been reported previously [Fukada, T., Hibi, M., Yamanaka, Y., Takahashi-Tezuka, M., Fujitani, Y., Yamaguchi, T., Nakajima, K. & Hirano, T. (1996) Immunity5, 449,460]. In contrast, we have recently demonstrated that the presence of a single STAT-recruitment site within gp130 is sufficient for IL-6- induced proliferation of Ba/F3 cells [Schmitz, J., Dahmen, H., Grimm, C., Gendo, C., Müller-Newen, G., Heinrich, P.C. & Schaper, F. (2000) J. Immunol.164, 848,854]. To unravel this discrepancy we analyzed the IL-6-induced dose-dependent proliferation of Ba/F3 cells mediated by receptor complexes lacking SHP2/SOCS3 recruitment sites. Surprisingly, pre-B cells, after stimulation with low amounts of IL-6, proliferate much more efficiently in the absence of the activated SHP2 than in the presence of the tyrosine phosphatase. Therefore, SHP2 activation appears to be relevant for IL-6-induced proliferation only after stimulation with very large amounts of IL-6. [source]

Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?

Marian C. Aldhous PhD
Abstract Background: Smoking differentially influences susceptibility to the inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC). We investigated the effects of nicotine on cytokine, cell cycle, and apoptotic responses in peripheral blood mononuclear cells (PBMCs) from IBD patients and healthy controls (HCs). Methods: PBMCs from IBD patients and HC were stimulated with lipopolysaccharide (LPS; 1 ,g/mL) or phytohemagglutinin (PHA, 5 or 0.5 ,g/mL), ± nicotine (1, 10, 100 ,g/mL). Cytokines (IL1,, IL2, IL10, IL12/IL23p40, TGF,, TNF,) were measured in supernatants at 24 hours. After 72 hours cells were analyzed by flow cytometry for cell cycle and apoptosis. Statistical modeling was used to identify interactions between cytokines and cell cycle / apoptosis and minimize confounding effects. Results: Stimulation by LPS and PHA (5 ,g/mL) increased IL12/IL23p40 production from CD and UC versus HC (P < 0.05); PHA (0.5 ,g/mL) increased IL1, in UC and decreased TGF, from CD and UC (P < 0.01). In all groups, nicotine reduced LPS- and PHA (0.5 ,g/mL)-stimulated production of IL1,, IL10, TGF,, and TNF, (P < 0.001). Cell cycle analysis showed that PHA, but not LPS, induced proliferation and decreased G0/G1 resting cells in CD and UC versus HC (P < 0.001). Nicotine decreased PHA-stimulated S-phase proliferation and increased G0/G1 resting cells (P < 0.01). Modeling showed independent associations between IL12/IL23p40 and apoptosis (P = 0.01), IL1, and resting cells (P = 0.006), TNF, and proliferating cells (P < 0.001). Disease activity and smoking habit had no effect. Conclusions: Dysregulated cytokine profiles in UC and CD are associated with specific alterations in cell cycle responses; these effects may be modified by nicotine, and potentially by anticytokine therapies. (Inflamm Bowel Dis 2008) [source]

Effects of isorhynchophylline on angiotensin II-induced proliferation in rat vascular smooth muscle cells

Feng Zhang
Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in cardiovascular diseases. Isorhynchophylline, an alkaloid from a traditional Chinese medicine Gambirplant, has been used to treat cardiovascular diseases. The aim of this study was to investigate the effects of isorhynchophylline on angiotensin II (Ang II)-induced proliferation of rat VSMCs. VSMCs were isolated from rat artery and cultured for 14 days before experimentation. The effect of isorhynchophylline on Ang II-induced proliferation was evaluated by cell number, MTT assay and flow cytometry, and nitric oxide (NO) content and activity of NO synthase (NOS) were measured. The expression of proto-oncogene c-fos, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) mRNAs was measured by real-time RT-PCR. VSMC cultures were verified by morphology and immunostaining with ,-smooth muscle actin. Isorhynchophylline (0.1,10.0 ,M) was not toxic to VSMCs, but markedly decreased Ang II (1.0 ,m)-enhanced cell number and MTT intensity, and blocked cell transition from G0/G1 to S phase. Furthermore, isorhynchophylline increased the NO content and NOS activity, and suppressed Ang II-induced over-expression of c-fos, OPN and PCNA. Thus, isorhynchophylline was effective against Ang-II induced cell proliferation, an effect that appears to be due, at least in part, to increased NO production, regulation of the cell cycle, and depressed expression of c-fos, OPN and PCNA related to VMSC proliferation. [source]

Proliferative alloresponse of T-cytotoxic cells identifies rejection-prone children with steroid-free liver transplantation

Chethan Ashokkumar
Donor-induced and third-party,induced proliferation of T-helper and T-cytotoxic (Tc) cells and their naļve and memory subsets was evaluated simultaneously in single blood samples from 77 children who received steroid-free liver transplantation (LTx) after induction with rabbit anti-human thymocyte globulin. Proliferation was measured by dilution of the intravital dye carboxyfluorescein succinimidyl ester (CFSE) in a 3- to 4-day mixed lymphocyte response coculture. The ratio of donor/third-party,induced proliferated (CFSElow) T-cells was reported as the immunoreactivity index (IR) for each subset. Rejectors were defined as those who experienced biopsy-proven acute cellular rejection within 60 days of the assay. IR > 1 signified increased risk of rejection, and IR < 1 implied decreased risk. Demographics for 32 rejectors and 45 nonrejectors were similar. Proliferated CFSElow T-cells and subsets were significantly higher among rejectors compared with nonrejectors. In 33 of 77 randomly selected children, logistic regression, leave-one-out cross-validation, and receiver operating characteristic analyses showed that the IR of Tc cells was best associated with biopsy-proven rejection (sensitivity > 75%, specificity > 88%). Sensitivity and specificity were replicated in the remaining 44 children who composed the validation cohort. IR of CFSElow Tc cells correlated significantly with IR of proinflammatory, allospecific CD154+ Tc cells (r = 0.664, P = 0.0005) and inversely with IR of allospecific, anti-inflammatory, cytotoxic T lymphocyte antigen 4,positive Tc cells (r = ,0.630, P = 0.007). In conclusion, proliferative alloresponses of Tc cells can identify rejection-prone children receiving LTx. Liver Transpl 15:978,985, 2009. © 2009 AASLD. [source]

Androgen receptor or estrogen receptor-, blockade alters DHEA-, DHT-, and E2 -induced proliferation and PSA production in human prostate cancer cells

THE PROSTATE, Issue 11 2007
Julia T. Arnold
Abstract BACKGROUND Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effectiveness and safety. LNCaP and LAPC-4 prostate cancer cells were used to determine whether DHEA-modulated proliferation and prostate specific antigen (PSA) production were mediated via the androgen receptor (AR) and/or ER,. METHODS Cells were treated with DHEA, DHT, or E2 and antagonists to AR (Casodex®-bicalutamide) or ER (ICI 182,780) or siRNA to the respective receptors. Proliferation was assessed by MTT assay and PSA mRNA and protein secretion were measured by quantitative real-time PCR and ELISA. Associations of AR and ER, were analyzed by co-immunoprecipitation studies and fluorescent confocal microscopy. RESULTS DHEA-, T-, and E2 -induced proliferation of LNCaP cells was blunted by Casodex but not by ICI treatment. In LNCaP cells, Casodex and ICI suppressed hormone-induced PSA production. In LAPC-4 cells, DHT-stimulated PSA mRNA was inhibited by Casodex and ICI, and the minimal stimulation by DHEA was inhibited by ICI. Use of siRNAs confirmed involvement of AR and ER, in hormone-induced PSA production while AR-ER, co-association was suggested by immunoprecipitation and nuclear co-localization. CONCLUSIONS These findings support involvement of both AR and ER, in mediating DHEA-, DHT-, and E2 -induced PSA expression in prostate cancer cells. Prostate 67: 1152,1162, 2007. © 2007 Wiley-Liss, Inc. [source]

Effect of L-carnitine on proliferative response and mRNA expression of some of its associated factors in splenic mononuclear cells of male broiler chicks

ABSTRACT The effect of L-carnitine supplementation on mitogen (concanavalin A, Con A) induced proliferation of mononuclear cells (MNC) in the spleen was investigated in broiler chickens at different ages. Day-old chickens were fed a diet supplemented with or without L-carnitine (100 ppm) for 24 days. The carnitine-supplemented group showed greater proliferation of MNC in the spleen in response to Con A than that of the control group at 24 days of age. In addition, at 24 days of age the carnitine-supplemented group showed higher expression of interleukin (IL)-2 and interferon (IFN)-, mRNA, but lower expression of inducible nitric oxide synthase (iNOS) in the Con A-stimulated splenic MNC than the control group. The enhancement effect of L-carnitine on MNC proliferation and IL-2 mRNA expression was not found in chicks at 14 days of age. Addition of L-carnitine (50 nmol/mL) to the culture medium enhanced proliferation and IL-2 mRNA expression of splenic MNC obtained from 24-day-old but not from 14-day-old broiler chickens. The results suggest that L-carnitine is capable of enhancing MNC proliferation in broiler chickens at 24 days of age partly through increasing IL-2 and IFN-, production and decreasing NO production. [source]

Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7,induced immune activation in rheumatoid arthritis

Sarita A. Y. Hartgring
Objective To evaluate the expression and functional ability of the high-affinity interleukin-7 receptor (IL-7R,) in patients with rheumatoid arthritis (RA). Methods Expression of IL-7R, and IL-7 was determined in synovial tissue from RA patients and was compared with that in synovial tissue from patients with undifferentiated arthritis (UA) and osteoarthritis (OA). IL-7R, expression on CD4 T cells, CD19 B cells, and CD14 monocyte/macrophages from RA synovial tissue, synovial fluid, and peripheral blood was also assessed. The proliferative capacity of IL-7R,bright and IL-7R,dim/, T cells was measured. In addition, we examined IL-7R blockade with soluble human IL-7R, (hIL-7R,) in the prevention of immune activation of peripheral blood mononuclear cells. Results We found significantly higher IL-7R, expression in RA and UA synovial tissue than in OA synovial tissue, and the level of IL-7R, expression correlated significantly with the levels of CD3 and IL-7 expression. CD4 T cells from RA synovial fluid and synovial tissue strongly expressed IL-7R,. A substantial percentage of B cells and macrophages from RA synovial fluid and synovial tissue also expressed IL-7R,, although less prominently than T cells. We found that peripheral blood IL-7R,bright T cells that did not express FoxP3 were highly proliferative as compared with IL-7R,dim/, T cells that did express high levels of FoxP3. Soluble hIL-7R, inhibited IL-7,induced proliferation and interferon-, production by mononuclear cells from RA patients. Conclusion Our data suggest that enhanced expression of IL-7R, and IL-7 in RA patients contributes significantly to the joint inflammation by activating T cells, B cells, and macrophages. The inhibition of IL-7R,mediated immune activation by soluble hIL-7R, further indicates an important role of IL-7R, in inflammatory responses in RA, suggesting IL-7R, as a therapeutic target for immunotherapy in RA. [source]

Interleukin-6 receptor superantagonist Sant7 inhibits TGF-,-induced proliferation of human lung fibroblasts

L. Gallelli
Therefore, the aim of this study was to investigate in primary cultures of normal and fibrotic human lung fibroblasts (HLF), exposed to either IL-6 or TGF-,1, the effects on phosphorylation of mitogen-activated protein kinases (MAPK) and cell growth of IL-6 signalling inhibition, performed by the IL-6 receptor superantagonist Sant7.Materials and methods:,MAPK phosphorylation was detected by Western blotting, HLF viability and proliferation were evaluated using the trypan blue staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively. Results:,Sant7, at a concentration of 1 µg/mL, was capable of significantly inhibiting HLF proliferation and MAPK phosphorylation induced by cell exposure to IL-6 (100 ng/mL) or TGF-,1 (10 ng/mL), whose actions were more evident in fibrotic cells. Conclusions:,These findings suggest that, in HLFs derived from patients with ILDs, the proliferative mechanisms activated by TGF-,1 are at least in part mediated by an increased release of IL-6, leading to phosphorylation-dependent MAPK activation. Such preliminary findings may thus open new therapeutic perspectives for fibrogenic ILDs, based on inhibition of signal transduction pathways stimulated by the IL-6 receptor. [source]

Expression and function of Toll-like receptor 9 in severely injured patients prone to sepsis

E. E. Baiyee
Summary The purpose of this prospective study was to enumerate Toll-like receptor 9 (TLR9)+ cells and measure their function using synthetic oligonucleotides enriched in CG dinucleotide motifs (CpG)-induced proliferation within 48 h after trauma in severely injured patients prone to sepsis. Sixteen consecutive trauma patients with an injury severity score (ISS) > 21 and 16 blood donors (controls) were included in this study. Using two-colour flow cytometry, TLR9 expression was detectable intracellularly and also on the surface of B lymphocytes. The surface expression of TLR9 of B lymphocytes from whole blood and peripheral blood mononuclear cells (PBMC) stimulated with CpG was significantly increased in B cells of severely injured patients prone to sepsis compared to controls. No significant differences could be observed between CpG-induced proliferation of PBMC of severely injured patients prone to sepsis and controls. As a measure of immunosuppression, human leucocyte antigen (HLA)-DR expression of monocytes of the trauma patients was significantly diminished compared with controls in PBMC and in whole blood. Immunosuppression in the early phase after trauma seems not to be associated with a disturbed sensing of bacterial DNA. [source]

In vivo immunomodulatory effects of dietary purple sweet potato after immunization in chicken

ABSTRACT This study was intended to determine the modulatory effects of dietary supplementation of purple sweet potato (Ipomoea batats Poir., PSP) on the immune response of chickens. PSP was included in a basal starter diet by 1% (PSPL) or 3% (PSPH) and continually fed. Newcastle disease (NDV) vaccine, Brucella abortus (BA) and sheep red blood cells (SRBC) were used for chicken immunization. Antibody titers against these antigens were used to estimate humoral immunity. Concanavalin A (Con A)-induced proliferations of splenocytes, thymocytes and peripheral blood lymphocytes (PBL), ratios of CD4- and CD8-single positive and CD4-CD8-double negative (DN) cells in splenocytes, were both used to indicate cellular immunity. Relative weights of spleen, thymus and bursa and white blood cell (WBC) counts were studied. PSPH increased anti-NDV (P < 0.05), anti-BA (P < 0.01) and anti-SRBC titers (P < 0.05) in response to secondary immunization, whereas PSPL increased titers of anti-BA (P < 0.05) and anti-SRBC (P < 0.01). Proliferations of splenocytes and thymocytes were augmented with PSPL (P < 0.05). PSPH -treated chickens had lower (P < 0.05) ratios of CD4-sigle positive lymphocytes. Proliferation of PBL, weights of lymphoid organs and WBC counts were not affected. These results suggest that dietary PSP supplementation could enhance the immune response after immunization in chickens. [source]