Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouth ulcers are one of the most common oral complaints. However, the association between oral ulceration and viruses and cytokines is uncertain. We detected the presence of human papilloma virus (HPV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV)-1, HSV-2 and human herpesvirus (HHV)-8 DNA in oral tissues by polymerase chain reaction (PCR) and Southern hybridization techniques, and quantified the serum levels of cytokines including interleukin (IL)-2, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), soluble Fas (sFas) and the Fas ligand (FasL) by enzyme-linked immunosorbent assay (ELISA) for 67 recurrent aphthous ulcer (RAU) patients and 72 normal individuals. Seven patient specimens were excluded from the study due to the negative PCR results for the beta-globin used as the internal control. Among the 32 (53.3%) virus-positive results from 60 patients' samples, 8 (13.3%) HPV, 4 (6.7%) HSV-1, 11 (18.3%) CMV, 9 (15.0%) EBV, and 16 (26.7%) HHV-8 samples proved to be positive. No HSV-2-positive samples were found. The percentage of single-virus infection (56.3%) was significantly greater than that of double-virus co-infection (31.3%) and the percentage of double-virus co-infection was significantly greater than the percentage of triple-virus co-infection (12.5%) (P < 0.05). In the 72 normal oral-tissue specimens, no viral DNA was detected. The mean serum cytokine level for patients was significantly (P < 0.05) greater than for controls for most of the separate age groups. The mean serum cytokine concentrations for the patient group demonstrated a diffuse pattern covering a wide range of serum concentrations, a very different result from the compact serum concentration pattern and lower mean serum cytokine concentrations revealed by the normal group. Overall association between viruses and recurrent aphthous ulceration is HHV-8 > CMV > EBV > HPV > HSV-1, regarding the frequency of prevalence (P < 0.05).
 ...
PMID:Study of the viral infections and cytokines associated with recurrent aphthous ulceration. 1584 Apr 65

To investigate the tumoricidal activity of dendritic cell (DC) stimulated by interferon-gamma (IFN-gamma) against freshly isolated myeloid leukemia cells and its mechanism, the peripheral blood monocytes collected from healthy donors were cocultured with interleukin-4 and granulocyte-macrophage colony-stimulating factor in medium to induce DC for 7 days. After 12 hour culture in the absence or presence of IFN-gamma, the changes of costimulatory molecules were analyzed with flow cytometry. To assay the cytotoxicity of DC against freshly isolated acute myeloid cells, they were cocultured at various effector-to-target ratio for 18 hours, then the percentage of tumoricidal activity was measured with (51)Cr release assay. To explore the mechanism of DC-mediated cytotoxicity, the change of DC surface or intracellular protein expression of Fas ligand (Fas L), TNF-alpha and TNF related apoptosis-inducing ligand (TRAIL) were analyzed with flow cytometry. The results showed that IFN-gamma enhanced cytotoxicity of DC against AML cells was (33.8 +/- 1.6)% at E:T as 20:1, compared with unstimulated DC (P < 0.05); IFN-gamma up-regulated expression of costimulatory molecules of DC surface such as CD86 and CD83; after stimulation with IFN-gamma, expression of intracellular TRAIL of DC was significantly enhanced, but expression of TRAIL on cell surface of DC was low; while the significant changes of Fas L and TNF-alpha expression neither on cell surface or in cells were not observed before or after stimulation with IFN-gamma. It is concluded that DC stimulated by IFN-gamma exhibit tumoricidal activity against AML cells. The cytotoxicity is partially related to maturation of DC and TRAIL inducing apoptosis, but not associated with death domain-independent mechanism of Fas L and TNF-alpha.
 ...
PMID:[Cytotoxicity of IFN-gamma-activated dendritic cells to freshly isolated acute myeloid leukemia cells]. 1640 83

Inflammatory stimuli, such as cytokines, can induce cyclooxygenase-2 (COX-2) expression in neutrophils. Selective, anti-inflammatory COX-2 inhibitors have been developed for patients with acute inflammatory diseases. Recent work has shown that selective COX-2 inhibitors interfere with tumor cell growth. The purpose of this study was to examine the capability of selective COX-2 inhibitors on Fas-mediated apoptosis in cytokine-stimulated neutrophils. Tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced prostaglandin E2 (PGE2) release through the induction of COX-2 in neutrophils. This effect was not seen with either interleukin (IL)-1beta or IL-8. TNF-alpha-and GM-CSF-induced PGE2 release was blocked by the addition of the selective COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide (NS-398; 1 microM). GM-CSF, IL-1beta and IL-8 suppressed Fas-mediated apoptosis in neutrophils; however, this effect was not seen with TNF-alpha. The anti-apoptotic effect of cytokines on Fas-mediated neutrophil apoptosis was attenuated by the addition of NS-398 (100 microM). These results suggest that NS-398 operates via two distinct mechanisms for regulating apoptosis and COX-2 activation in neutrophils. This distinction is indicated by the difference in concentration of NS-398 required for acceleration of Fas-mediated neutrophil apoptosis, and the inhibition of PGE2 synthesis. Moreover, NS-398 suppressed the anti-apoptotic activity of IL-8 and IL-1beta, but did not induce COX-2; therefore, the pro-apoptotic mechanism of the selective COX-2 inhibitor may be unrelated to COX-2 activity. Thus, a selective COX-2 inhibitor may contribute to the reduction of acute inflammation through the enhancement of neutrophil apoptosis.
 ...
PMID:Accelerative effect of a selective cyclooxygenase-2 inhibitor on Fas-mediated apoptosis in human neutrophils. 1642 68

Human monocyte-derived dendritic cells (DCs), stimulated with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 1 week, major histocompatibility complex killed human tumor cells in 24-hour cytotoxicity assays. These immature DCs were >90% CD11c, major histocompatibility complex class II(+), but <1% were CD83(+) cells. Within 24 hours, these DCs ingested tumor membranes. The DC cells also lysed Jurkat lymphoma cells, but not Jurkat cells genetically knocked out of the Fas-associated death domain (FADD) or caspase-8. DC2.4, a cloned murine DC line, also displayed cytotoxicity toward U-251 cells, although these murine DCs were less potent than human DC. DC2.4 did not kill Jurkat cells, rat T9 glioma cells, or human Caco-2 colon cancer cells, suggesting that a unique receptor or ligand interaction exists between the DC and U-251 cells. This interaction was destroyed by the paraformaldehyde fixation of the tumor cells. Supernatants from the cultures of DC2.4 and tumor cells were analyzed by the Griess reaction for signs of nitric oxide (NO) production. Augmented NO production occurred in DC2.4/U-251 and DC2.4/Jurkat cultures but was not seen in the human DC/U-251 cultures. These studies suggest that DCs possess different mechanisms of tumoricidal activity.
 ...
PMID:Human allogeneic and murine xenogeneic dendritic cells are cytotoxic to human tumor cells via two distinct pathways. 1797 70

The study was aimed to investigate the influence of interferon alpha (IFN-alpha) on the expressions of Fas and Fas ligand (FasL) in dendritic cells (DCs) from patients with chronic myeloid leukemia (CML). In addition to adding stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha) and interleukin 4 (IL-4), the IFN-alpha was added to the serum-free medium for DCs. After culturing for 10 - 14 days, cell phenotype and percentage of Ph(1) chromosome were detected by different methods. The expression of Fas or FasL on CML-DCs and cell cycle of DCs labeled with propidium iodine (PI) were measured by flow cytometry. The concentration of sFas in supernatants was analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicated that the expression of co-stimulatory molecules were improved significantly while the percentages of Ph(1) positive cells decreased. The level of Fas on cells was up-regulated and the concentration of sFas decreased. However, the expression of FasL was negative. The ratio of apoptosis rose gradually while the concentration of IFN-alpha increased. It is concluded that IFN-alpha can accelerate the apoptosis of Ph(1) positive cells through Fas/FasL pathway, so the number of Ph(1) negative cells increases relatively.
 ...
PMID:Influence of interferon alpha on expression of Fas and Fas ligand in dendritic cells from patients with chronic myeloid leukemia. 1854 17

Apoptosis of human neutrophils is a crucial mechanism for the resolution of inflammation. We previously showed that insulin-like growth factor-1 (IGF1) delays spontaneous neutrophil apoptosis without influencing the secretion of cytokines by these cells. In the present study, we further addressed the role of IGF1 in regulating neutrophil survival in the presence of other factors present during inflammation, and the mechanism involved in delaying apoptosis. We show that IGF1 delays neutrophil apoptosis triggered by the agonistic anti-Fas antibody CH11 and that the effect of IGF1 is comparable in magnitude to that of the acknowledged anti-apoptotic cytokines interferon-gamma (IFNG) and granulocyte-macrophage colony-stimulating factor (GM-CSF; now known as CSF2). Furthermore, IGF1 exerted additional effects on cell survival in the presence of these cytokines. IGF1 did not affect Fas expression or activation by anti-Fas of caspase-8, but inhibited the depolarization of the mitochondrial membrane. Inhibitor studies indicate that the phosphatidylinositol-3 kinase (PI3K) pathway, but not the MEK-ERK pathway, mediates the effects of IGF1. However, in contrast to CSF2, IGF1 did not induce phosphorylation and translocation to the membrane of AKT, the canonical downstream target of PI3K. We therefore speculate that other downstream targets of PI3K are involved in the delay of neutrophil apoptosis by IGF1, possibly through stabilization of the mitochondrial membrane.
 ...
PMID:Insulin-like growth factor-1 delays Fas-mediated apoptosis in human neutrophils through the phosphatidylinositol-3 kinase pathway. 1865 23

Pneumocystis infections increase host susceptibility to additional insults that would be tolerated in the absence of infection, such as hyperoxia. In an in vivo model using CD4-depleted mice, we previously demonstrated that Pneumocystis murina pneumonia causes significant mortality following an otherwise nonlethal hyperoxic insult. Infected mice demonstrated increased pulmonary inflammation and alveolar epithelial cell apoptosis compared to controls. To test the mechanisms underlying these observations, we examined expression of components of the Fas-Fas ligand pathway in P. murina-infected mice exposed to hyperoxia. Hyperoxia alone increased expression of Fas on the surface of type II alveolar epithelial cells; conversely, infection with P. murina led to increased lung expression of Fas ligand. We hypothesized that inhibition of inflammatory responses or direct inhibition of alveolar epithelial cell apoptosis would improve survival in P. murina-infected mice exposed to hyperoxia. Mice were depleted of CD4(+) T cells and infected with P. murina and then were exposed to >95% oxygen for 4 days, followed by return to normoxia. Experimental groups received vehicle, dexamethasone, or granulocyte-macrophage colony-stimulating factor (GM-CSF). Compared with the vehicle-treated group, treatment with dexamethasone reduced Fas ligand expression and significantly improved survival. Similarly, treatment with GM-CSF, an agent we have shown protects alveolar epithelial cells against apoptosis, decreased Fas ligand expression and also improved survival. Our results suggest that the dual stresses of P. murina infection and hyperoxia induce lung injury via activation of the Fas-Fas ligand pathway and that corticosteroids and GM-CSF reduce mortality in P. murina-infected mice exposed to hyperoxic stress by inhibition of inflammation and apoptosis.
 ...
PMID:Critical roles of inflammation and apoptosis in improved survival in a model of hyperoxia-induced acute lung injury in Pneumocystis murina-infected mice. 1912 1

Eosinophils have been implicated in allergic diseases, such as bronchial asthma, which is characterized by elevated eosinophil numbers in the bronchoalveolar lavage fluid and peripheral blood. Their accumulation and activation within the airway mucosa is thought to cause tissue injury, contraction of airway smooth muscle, and increased bronchial responsiveness (1-3). The balance between cell maturation and death is of great importance in determining the number of eosinophils in the blood and tissues (4-6). Following in vitro culture in the absence of cytokines, eosinophils undergo apoptosis, or programmed cell death (7,8), a process that can be inhibited by cytokines such as interleukin-3 and -5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), and accelerated by such factors as corticosteroids and Fas (7-11).
 ...
PMID:Human eosinophil isolation and the measurement of apoptosis. 2131 24

Colony-stimulating factor-1 (CSF-1), the principal growth factor for macrophages, is increased in the kidney, serum, and urine of patients with lupus nephritis, and eliminating CSF-1 suppresses lupus in MRL-Fas(lpr) mice. CSF-1 has three biologically active isoforms: a membrane-spanning cell surface glycoprotein (csCSF-1), a secreted proteoglycan (spCSF-1), and a secreted glycoprotein (sgCSF-1); the role of each isoform in the circulation and kidney in autoimmune disease is not well understood. Here, we constructed mutant MRL-Fas(lpr) mice that only express csCSF-1 or precursors of the spCSF-1 and sgCSF-1 isoforms. Both csCSF-1 and spCSF-1 shifted monocytes toward proinflammatory, activated populations, enhancing their recruitment into the kidney during lupus nephritis. With advancing lupus nephritis, spCSF-1 was the predominant isoform responsible for increasing circulating CSF-1 and, along with the csCSF-1 isoform, for increasing intrarenal CSF-1. Thus, csCSF-1 appears to initiate and promote the local activation of macrophages within the kidney. Intrarenal expression of csCSF-1 and spCSF-1 increases with advancing nephritis, thereby promoting the intrarenal recruitment of monocytes and expansion of Ly6C(hi) macrophages, which induce apoptosis of the renal parenchyma. Taken together, these data suggest that the three CSF-1 isoforms have distinct biologic properties, suggesting that blocking both circulating and intrarenal CSF-1 may be necessary for therapeutic efficacy.
 ...
PMID:Distinct roles of CSF-1 isoforms in lupus nephritis. 2188 70

Currently, no early pregnancy marker has been identified in the bitch. However, significantly decreased concentrations of heat-shock protein (HSP) 70 and increased activity of matrix metalloproteinases (MMP) 2,9 were detected in serum from bitches during the pre-implantation period between days 5 and 13 after mating, that is, 2-3 days after ovulation as determined by the measurement of progesterone and vaginal cytology. Especially during the implantation period and thereafter (days 15-55), high serum concentrations of antibodies against desmin are present, which is believed to indicate or regulate decidualization. Pre-implantation embryos express mRNA for enzymes and cytokines, known to promote and regulate trophoblast growth, and some intrauterine changings like the increased activity of MMP 2,9 in maternal endometrium are dependant on the presence of embryos. Some mechanisms that protect canine embryos from attack by the maternal immune system can also be identified. The embryos express CD4, a receptor known to interact with immune cells. They, furthermore, do not express MHC I and II, which might prevent them from being recognized as foreign antigen. Pre-implantation embryos express FasL, which probably renders them able to destroy Fas-bearing cytotoxic T cells. Furthermore, the uterus during pre-implantation and implantation expresses cytokines that modulate the intrauterine milieu towards a predominance of Th2 cells. During pre-implantation and implantation, an increased uterine expression of platelet activating factor (PAF) and PAFR, vascular endothelial growth factor (VEGF) and EGFR2 as well as epithelial growth factor (EGF) is characteristic. Towards placentation, the upregulation of leukaemia inhibiting factor (LIF) and at placentation the expression of insulin-like growth factor(IGF)2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are striking. Progesterone receptor (PR) appears to be downregulated inside the uterus except at placentation sites, presumably where it is essential for maintenance of pregnancy. In addition, receptor-bound P4 regulates the activity of MMP 2,9. Apoptosis seems to be a further regulatory mechanism. Expression of Fas and FasL mRNA in uterine tissue is maximum until implantation, both factors then decreased significantly. These changings might indicate increased endometrial apoptosis and defence against maternal cytotoxic T cells, probably promoting trophoblast invasion. In human decidual stromal cells, GnRH is involved in the regulation of apoptosis, which is proposed to be similar in pregnant bitches, as GnRH-R is expressed at canine implantation sites. Our work investigating immunological changes in pregnant bitches has elucidated aspects of the complex physiology of implantation but raises important questions about the mechanisms involved.
 ...
PMID:Early canine pregnancy--a battle for successful growth and angiogenesis. 2327 90


<< Previous 1 2 3 4 5 Next >>