Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q15004 (PAF)
 2,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present work we review the existing evidence for a LPS-induced cytokine-mediated eosinophil accumulation in a model of acute inflammation. Intrathoracic administration of LPS into rodents (mice, rats or guinea pigs) induces a significant increase in the number of eosinophils recovered from the pleural fluid 24 hr later. This phenomenon is preceded by a neutrophil influx and accompanied by lymphocyte and monocyte accumulation. The eosinophil accumulation induced by LPs is not affected by inhibitors of cyclo or lipoxygenase nor by PAF antagonists but can be blocked by dexamethasone or the protein synthesis inhibitor cycloheximide. Transfer of cell-free pleural wash from LPS injected rats (LPS-PW) to naive recipient animals induces a selective eosinophil accumulation within 24 hr. The eosinophilotactic activity present on the LPS-PW has a molecular weight ranging between 10 and 50 kDa and its effect is abolished by trypsin digestion of the pleural wash indicating the proteic nature of this activity. The production of the eosinophilotactic activity depends on the interaction between macrophages and T-lymphocytes and its effect can not be blocked by anti-IL-5 monoclonal antibodies. Accumulated evidence suggest that the eosinophil accumulation induced by LPS is a consequence of a eosinophilotactic cytokine produced through macrophage and T-cell interactions in the site of a LPS-induced inflammatory reaction.
 ...
PMID:A role for lymphocytes and cytokines on the eosinophil migration induced by LPS. 969 33

Contact lens induced acute red eye (CLARE) and contact lens induced peripheral ulcer (CLPU) are among the most common contact lens induced inflammatory reactions. Both CLARE and CLPU are characterized by corneal infiltration which indicates the presence of chemoattractants and other inflammatory mediators. The aim of this study was to characterize the cytokine and chemotactic lipid inflammatory mediator profile in the tears of people experiencing CLARE or CLPU. Cytokines IL-1 beta, IL-6, IL-8, GM-CSF and LTB4 in tears were measured by antibody sandwich and competition inhibition enzyme-linked immunosorbent assays (ELISA). Platelet activating factor-like activity was measured by a degranulation assay by measuring the release of labelled serotonin from platelets. The functional role GM-CSF and chemoattractants were determined by flow cytometry and chemotaxis. Increased levels of cytokines and chemoattractants were detected in both CLARE and CLPU tears. CLPU tears showed increased levels of LTB4 (P = 0.002) and PAF-like activity (P = 0.047) whereas CLARE tears showed increased levels of GM-CSF (P = 0.002). IL-8 (P < 0.05). LTB4 (P = 0.002) and PAF-like activity (P = 0.047) compared to control tears. Flow cytometric analysis revealed that incubation of PMN with CLARE tears increased the number of IgA receptors indicating that the GM-CSF in CLARE tears was active. Combinations of suboptimal concentrations (which were found in CLARE and CLPU tears) of IL-8 with either LTB4 or PAF significantly (P < 0.0001) enhanced the chemotactic activity for PMN compared to their individual effects. Our data highlight the possible pathophysiological roles of these inflammatory mediators in leukocyte recruitment and activation during ocular inflammatory responses. The results suggests that GM-CSF, IL-8 and LTB4 are active during corneal pathology and LTB4 or IL-8 may maintain the contact lens induced PMN response in vivo.
 ...
PMID:Cytokine and lipid inflammatory mediator profile of human tears during contact lens associated inflammatory diseases. 970 74

Oxidized low-density lipoprotein (oxLDL) consists of both lipid components and apoprotein B100. OxLDL has both proinflammatory and cytotoxic properties. The present study was undertaken to investigate the effects of components in the lipid moiety of oxLDL on immune activation as determined by cytokine and immunoglobulin secretion. LPC induced interferon-gamma (IFN-gamma) secretion in peripheral blood mononuclear leucocytes from healthy blood donors. The effect varied between individuals, and there were both responders and non-responders. Furthermore, LPC induced enhanced antibody production, indicating B cell activation. None of eight oxysterols, arachidonic acid (AA), or 15-lipoxygenase products of AA tested had immune stimulatory properties. We recently demonstrated that PAF and oxLDL induce IFN-gamma secretion by a common mechanism. LPC-induced IFN-gamma secretion was inhibited by a specific PAF receptor antagonist, WEB 2170, indicating that the PAF receptor is involved in LPC-induced immune activation. Both oxLDL- and LPC-induced antibody formation was inhibited by WEB 2170. Furthermore LPC also induced tumour necrosis factor-alpha secretion, and this effect was inhibited by WEB 2170. LPC is produced during lipid oxidation (as in oxLDL), but also by enzymes such as phospholipase A2. The findings indicate that LPC may play an important role in inflammatory reactions, including atherosclerosis.
 ...
PMID:Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism. 1033 26

Although preimplantation embryo and decidual cells secrete significant amounts of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF); its precise function in early pregnancy has yet to be established. To investigate the effect of PAF on cytokine synthesis, we measured the cytokine concentration in the culture media of two human cell lines: normal endometrial stromal cells (ESC) and endometrial stromal sarcoma cells (MaMi), following stimulation with a non-metabolized PAF analogue, carbamyl-PAF (C-PAF). Enzyme-linked immunosorbent assays were used to measure five cytokines: interleukin (IL)-6, IL-8, macrophage colony-stimulating factor (M-CSF), macrophage inflammatory protein-1alpha (MIP-1alpha) and tumour necrosis factor-alpha (TNF-alpha). We also evaluated the mRNA expression for IL-6 and IL-8 in ESC after C-PAF stimulation using Northern blot analysis. Non-stimulated ESC and MaMi cells both secreted IL-6, IL-8, and M-CSF, but not MIP-1alpha or TNF-alpha. The concentrations of IL-6, IL-8, M-CSF, MIP-1alpha, and TNF-alpha in the culture media of both cell lines increased in parallel with increasing amounts of C-PAF. C-PAF stimulated IL-6 and IL-8 transcription in ESC. These results suggest that PAF secretion by decidual tissues and developing embryos may induce cytokine synthesis by the ESC, as part of the cytokine network in the feto-maternal unit. An increase in the local cytokine concentration may be an important factor in the maintenance of early stages of gestation.
 ...
PMID:Platelet-activating factor stimulates cytokine production by human endometrial stromal cells. 1034 Oct 2

Bone marrow stromal cells regulate marrow haematopoiesis by secreting interleukins (IL) such as IL-8. Lipid mediators modulate IL-8 synthesis in numerous cell types. We have investigated the effects of 5 lipid mediators (PAF, PGE(2), LTB(4), 12-HETE and 15-HETE) on the spontaneous and cytokine-induced IL-8 synthesis by human bone marrow stromal cells. By using reverse-transcriptase polymerase chain reaction (RT-PCR) we demonstrate that these cells constitutively express IL-8 transcripts. By using a specific ELISA, we found that the production of IL-8 by marrow stromal cells is enhanced after stimulation with 12-HETE (1 microM) both in serum-free and serum-containing culture medium. LTB(4)(1 microM) enhances IL-8 production only in serum-supplemented medium. PAF, PGE(2)and 15-HETE (1 microM to 0.1 nM) have no effect on the spontaneous and serum-induced production of IL-8 by human bone marrow stromal cells. PGE(2)(1 microM or 10 nM) reduces marrow stromal cell IL-8 synthesis in response to IL-1alpha or TNF-alpha. In contrast, PAF, 12-HETE, 15-HETE and LTB(4)have no effect. In conclusion, various lipid mediators modulate the spontaneous, serum- or cytokine-induced IL-8 synthesis by bone marrow stromal cells, highlighting, for the first time, their potential role in the regulation of IL-8 production within the human bone marrow.
 ...
PMID:Lipid mediators modulate the synthesis of interleukin 8 by human bone marrow stromal cells. 1043 8

Partial-thickness skin burns have been shown to induce neutrophil-dependent microvascular injury both locally (skin) and systemically (lung). In the present study, interventional measures to block inflammatory chemoattractants were employed to define the pathophysiologic role of these mediators in the development of secondary lung injury following thermal injury of skin. Rats were treated with blocking antibodies to either C5a or to the alpha-chemokines, keratinocyte-derived cytokine (KC), or macrophage inflammatory protein-2 (MIP-2). To study the role of platelet activating factor, a receptor antagonist (PAF-Ra) was utilized. The development of lung vascular injury following thermal injury to skin was significantly attenuated by treatment with anti-C5a (84%), anti-KC (67%), and anti-MIP-2 (77%), but treatment with PAF-Ra had no protective effects. Protective interventions were paralleled by significant reductions in the tissue buildup of myeloperoxidase. When bronchoalveolar lavage fluids from thermally injured rats were evaluated, elevations in TNF;ZA and IL-1 were found and were determined to be C5a-dependent (but unaffected by treatment with PAF-Ra). These studies indicate that lung tissue injury after thermal skin burns is dependent on chemotactic mediators. The data also suggest that lung expression of TNFalpha and IL-1 after thermal injury of skin is C5a-dependent.
 ...
PMID:Chemotactic mediator requirements in lung injury following skin burns in rats. 1048 40

At the site of acute inflammation, leukocytes are confronted with multiple mediators which are expected to modulate each other with respect to cell responses to the individual ligand. In the present study, we compared the effects of the classical chemoattractants FMLP, PAF and LTB4, of the chemokine IL-8 and of TNFalpha, GM-CSF, IFN-gamma and IL-1beta on C5a-induced chemotaxis, degranulation, oxidative burst and expression of adhesion molecules of human neutrophils in vitro. Upon preincubation, TNFalpha as well as GM-CSF dose-dependently inhibited C5a-mediated chemotaxis, but augmented the release of elastase as well as respiratory burst activity. The effects of the two cytokines were accompanied by a downregulation of C5a receptors as determined by Scatchard analysis using (125)I-labeled C5a. Compared on a molar basis, TNFalpha was more effective than GM-CSF. C5a-induced expression of beta(2)-integrins was only moderately influenced by TNFalpha and GM-CSF. C5a itself diminished chemotaxis as well as degranulation and oxidative burst in response to a second dose of the same ligand (homologous desensitization), whereas heterologous desensitization by FMLP and IL-8 was restricted to C5a-induced degranulation or not observed (PAF, LTB4]. The cytokine effects are likely to be a consequence of altered C5a receptor expression as well as of postreceptor events. In concert with C5a, certain cytokines may shift neutrophil effector functions from migration to exocytosis, an essential step within the sequence of events in a coordinated inflammatory response.
 ...
PMID:Modulation of C5a-mediated effector functions of human polymorphonuclear leukocytes by tumor necrosis factor alpha and granulocyte macrophage colony-stimulating factor. 1057 75

This study investigates the production of interleukin (IL-)1beta by cultured human bone marrow stromal cells. RT-PCR experiments indicate that two-thirds of cultures constitutively express IL-1beta mRNA transcripts. Their cell-associated IL-1beta levels are elevated after stimulation with tumour necrosis factor (TNF-)alpha but not with cytokines such as IL-1alpha, IL-3, IL-4, IL-6, IL-7, IL-10, SCF, G-CSF, M-CSF and TGF-beta or lipid mediators such as PGE2, LTB4, LXA4, LXB4, 12-HETE, 15-HETE and PAF. Addition of IL-4, but not IL-10 or TGF-beta, reduces the TNF-alpha-induced cell-associated IL-1beta. IL-1beta is never detected in bone marrow stromal cell supernatants whatever the stimulant added. In conclusion the pro-inflammatory molecule TNF-alpha stimulates bone marrow stromal cell-associated IL-1beta levels while the anti-inflammatory cytokine IL-4 reduces the TNF-alpha-induced effect. These results strengthen the key regulatory role of IL-4 on the production of haematopoietic cytokines by human bone marrow stromal cells.
 ...
PMID:Effect of cytokines and lipid mediators on the synthesis of interleukin 1 beta by human bone marrow stromal cells. 1085 67

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) and its receptor are known to play important roles in modulating neuronal plasticity and inflammatory responses, particularly during neuronal injury. PAF receptors are widespread in different brain regions and are present on the cell surface as well as in intracellular membrane compartments. Astrocytes are immune active cells and are responsive to cytokines, which stimulate signaling cascades leading to transcriptional activation of genes and protein synthesis. Our recent studies indicate the ability of cytokines, e.g., tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) and interferon-gamma (IFNgamma), to induce the inducible nitric oxide (iNOS) and secretory phospholipase A2 (sPLA2) genes in immortalized astrocytes (DITNC) (Li et al., J. Interferon and Cytokine Res. 19: 121-127. 1999). The main objective for this study is to examine the effects of PAF antagonists on cytokine induction of iNOS and sPLA2 in these cells. Results show that BN50730, a synthetic PAF antagonist, but not BN52021, a natural PAF antagonist (ginkolide B) can dose-dependently inhibit cytokine induction of NO production and sPLA2 release. Inhibition of NO production by BN50730 corroborated well with the decrease in iNOS protein and mRNA levels as well as binding of NF-kappaB STAT- 1 to DNA, suggesting that BN50730 action is upstream of the transcriptional process. These results are in agreement with the role of intracellular PAF in regulating the cytokine signaling cascade in astrocytes and further suggest the possible use of BN50730 as a therapeutic agent for suppressing the inflammatory pathways elicited by cytokines.
 ...
PMID:Platelet activating factor (PAF) antagonists on cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC). 1090 22

Various mechanisms may contribute to the antiatherogenic potential of apolipoprotein A-I (apo A-I) and high density lipoproteins (HDLs). Therefore, the effect of adenovirus-mediated human apo A-I gene transfer or human apo A-I transgenesis on platelet-activating factor acetylhydrolase (PAF-AH) and arylesterase/paraoxonase (PON1) was studied in C57BL/6 and C57BL/6 apo E(-/-) mice. Human apo A-I transgenesis in C57BL/6 mice resulted in a 4.2-fold (P<0.0001) increase of PAF-AH and a 1.7-fold (P=0.0012) increase of PON1 activity. The apo E deficiency was associated with a 1.6-fold (P=0.008) lower PAF-AH and a 2.0-fold (P=0.012) lower PON1 activity. Human apo A-I transgenesis in C57BL/6 apo E(-/-)mice increased PAF-AH and PON1 activity by 2.1-fold (P=0.01) and 2.5-fold (P=0.029), respectively. After adenovirus-mediated gene transfer of human apo A-I into C57BL/6 apo E(-/-)mice, a strong correlation between human apo A-I plasma levels and PAF-AH activity was observed at day 6 (r=0.92, P<0.0001). However, PON1 activity failed to increase, probably as a result of cytokine-mediated inhibition of PON 1 expression. In conclusion, this study indicates that overexpression of human apo A-I increases HDL-associated PAF-AH activity. PON1 activity was also increased in human apo A-I transgenic mice, but not after human apo A-I gene transfer, a result that was probably related to cytokine production induced in the liver by the adenoviral vectors. Increased levels of these HDL-associated enzymes may contribute to the anti-inflammatory and antioxidative potential of HDL and thereby to the protection conferred by HDL against atherothrombosis.
 ...
PMID:Effect of overexpression of human apo A-I in C57BL/6 and C57BL/6 apo E-deficient mice on 2 lipoprotein-associated enzymes, platelet-activating factor acetylhydrolase and paraoxonase. Comparison of adenovirus-mediated human apo A-I gene transfer and human apo A-I transgenesis. 1103 Dec 26


<< Previous 1 2 3 4 5 6 7 Next >>