Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue factor pathway inhibitor (TFPI) is the primary physiological inhibitor that regulates tissue factor-induced blood coagulation. TFPI is thought to be synthesized, in vivo, primarily by microvascular endothelial cells. Little is known about how TFPI is regulated under pathophysiological conditions. In this study, we determined mechanisms by which TFPI expression is regulated by human pulmonary artery smooth muscle cells (PASMC), because these cells contribute to remodeling of the pulmonary vasculature in disease. PASMC in culture constitutively synthesize and secrete TFPI. Exposure of PASMC to phorbol myristate acetate, lipopolysaccharide, tumor necrosis factor alpha, thrombin, interleukin-1, and transforming growth factor-beta had no significant effect on expression of TFPI by PASMC. By contrast, treatment of PASMC with serum and basic fibroblast growth factor (bFGF)/heparin markedly upregulated the expression of TFPI activity and antigen. On Western blot analysis, a protein consistent with full-length TFPI (42 kD) was identified in the conditioned media of PASMC, and the levels of the protein were much higher in the conditioned media of serum and bFGF/heparin-treated cells. Northern blot analysis showed that PASMC constitutively express TFPI mRNA, and treatment of cells with serum and bFGF/heparin had a minimal effect on the steady-state levels of TFPI mRNA. Nuclear run-on analysis did not show a significant increase in the transcriptional rate of TFPI gene in PASMC treated with serum or bFGF/heparin. Cycloheximide, but not actinomycin-D, treatment inhibited the serum and bFGF/heparin-induced increase in TFPI activity in PASMC. In conclusion, our data demonstrate that PASMC constitutively synthesize and secrete TFPI and serum or bFGF upregulate its expression, suggesting that growth factors that can stimulate the vessel wall in vivo might locally regulate TFPI expression. Our study also suggests that control of TFPI expression by serum or bFGF occurs via translational rather than transcriptional regulation.
 ...
PMID:Regulation of tissue factor pathway inhibitor expression in smooth muscle cells. 1039 25

This study was designed to investigate VEGF production from peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) compared with healthy controls and to identify the predominant cellular source in PBMC isolated from RA patients. The regulation of PBMC VEGF production by cytokines and synovial fluid (SF) was studied. PBMC were isolated from RA patients and healthy controls and stimulated with lipopolysaccharide (LPS), IL-1beta, IL-4, IL-6, IL-8, IL-10, TNF-alpha and transforming growth factor-beta (TGF-beta) isoforms for varying time points up to 72 h at 37 degrees C/5% CO2. The effect of SF on VEGF secretion by PBMC was also studied. Supernatant VEGF levels were measured using a flt-1 receptor capture ELISA. RA patients had significantly higher spontaneous production of VEGF compared with controls, and monocytes were identified as the predominant cellular source. RA PBMC VEGF production was up-regulated by TGF-beta isoforms and TNF-alpha and down-regulated by IL-4 and IL-10, with no effect observed with IL-1beta, IL-6 and IL-8. Antibody blocking experiments confirmed that TNF-alpha and not TGF-beta isoforms in SF increased VEGF secretion by RA PBMC. These results emphasize the importance of monocytes as a source of VEGF in the pathophysiology of RA. Several cytokines known to be present in SF can modulate the level of VEGF secretion, but the predominant effect of SF in VEGF up-regulation is shown to be dependent on TNF-alpha.
 ...
PMID:Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): specific up-regulation by tumour necrosis factor-alpha (TNF-alpha) in synovial fluid. 1040 32

Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor abundantly found in mucous secretions of lung, is thought to serve as an important protective component in the secretory fluids at sites of degenerative and inflammatory diseases. In this study, we examined the effects of SLPI on the production of a proinflammatory cytokine, TNF-alpha, and immunosupressive cytokines, IL-10 and transforming growth factor-beta (TGF-beta) by macrophages (M phi s), in response to lipopolysaccharide (LPS)-mediated stimulation and M. avium complex (MAC) infection, using recombinant half-sized SLPI (1/2 SLPI) consisting of C-terminal domain (Arg55-Ala107) of intact SLPI. In addition, effects of SLPI on the production of nitric oxide radicals (NO), important antimicrobial effectors of M phi s against micro-organisms, by these M phi s were studied. First, when the number of TNF-alpha producing cells in the LPS-stimulated M phi population was counted by the ELISPOT assay, more than half of the M phi s acquired TNF-alpha secreting ability at 24 hr after LPS stimulation. On the other hand, MAC-infected M phi s produced detectable amounts of TNF-alpha into culture fluid during the first 24 hr. In both cases, 1/2 SLPI did not affect the LPS- or MAC-induced TNF-alpha production by M phi s. Second, when the production of IL-10 and TGF-beta by M phi s was determined by measuring the amounts of these cytokines accumulated in M phi culture fluids by ELISA, the following was observed. M phi IL-10 production was rapidly increased in the early phase of cultivation after LPS stimulation or MAC infection, peaking on day 1 and thereafter declining to normal level by day 14. Half-sized SLPI did not affect IL-10 production of LPS-stimulated M phi s, while it caused slight enhancement of IL-10 production by MAC-infected M phi s. M phi TGF-beta production was initiated in the middle phase (day 7) of M phi cultivation and continued until day 14. Notably, 1/2 SLPI markedly potentiated the TGF-beta producing ability of the LPS-stimulated M phi s. Moreover, 1/2 SLPI caused moderate increase in the TGF-beta production by MAC-infected M phi s. Third, significantly potentiated NO production was observed in M phi s during the first 2 days after LPS stimulation and MAC infection. Half-sized SLPI did not affect the NO production by LPS-stimulated or MAC-infected M phi s. These findings indicate that SLPI up-regulates the production of some immunoregulatory cytokines including IL-10 and TGF-beta, particularly the latter, by M phi s in response to LPS stimulation or MAC infection, thereby suggesting the possibility that SLPI may exhibit antiinflammatory effects in vivo, especially patients with bacterial infections including MAC diseases, through the modulation of M phi expression of some immunosuppressive cytokines.
 ...
PMID:[Effects of secretory leukocyte protease inhibitor on the production of some cytokines and nitric oxide by murine peritoneal macrophages in response to lipopolysaccharide stimulation and M. avium complex infection]. 1048 11

The differences between cytokine-producing profiles of activated macrophages (A-M phi) and suppressor macrophages (S-M phi) were examined. A-M phi, which exhibited cytotoxicity against RK-13 cells, were generated from resident rabbit alveolar M phi by treatment with lymphokine solution (culture fluids of rabbit spleen cells stimulated with concanavalin A [Con A]). S-M phi, which were able to inhibit cellular proliferations of rabbit spleen cells stimulated with Con A, were generated from resident alveolar M phi by treatment with 1-methyladenosine (an immunosuppressive molecule in tumourous ascites fluids). When A-M phi were stimulated with lipopolysaccharide (LPS) in vitro, the cells produced significantly more interleukin (IL)-1 (approximately 1.4 times), IL-6 (approximately 2.1 times), IL-12 (approximately 60 times), and tumour necrosis factor-alpha (TNF-alpha) (approximately 37 times) than did resting macrophages (R-M phi) stimulated with LPS as control cells. After the stimulation with LPS, both A-M phi and R-M phi did not produce transforming growth factor-beta (TGF-beta). In contrast, when S-M phi were stimulated with LPS in vitro, the cells produced significantly more TGF-beta (approximately 1.6 times) and significantly less IL-6 (approximately 1.8 times) than did control cells. Also, S-M phi did not produce IL-1, IL-12, and TNF-alpha into their culture fluids after the stimulation with LPS. These results show the differences between cytokine-producing profiles of A-M phi and S-M phi, and characteristics of their cytokine-producing profiles are analogous to T cell subsets. Differences displayed in the cytokine profiles may contribute to the effector (A-M phi) or the suppressor (S-M phi) functions of alveolar M phi.
 ...
PMID:Cytokine production by rabbit alveolar macrophages: differences between activated and suppressor cell phenotypes. 1052 98

Selected phosphorothioate oligodeoxynucleotides containing CpG (CpG-ODN) activate immune responses, including immunoglobulin synthesis, B cell proliferation, and cytokine production by monocytes. We examined the effect of a CpG-ODN (#1760) on the adhesion of macrophages derived from human blood monocytes in vitro. CpG-ODN (6 microg/mL) completely inhibited the adherence of macrophages to plastic or glass during 7 or more days of culture. A non-CpG control ODN (#1814) was without effect. Two other CpG-ODNs (#1826 and #1842) also completely inhibited macrophage adherence. The specific inhibitor of CpG-ODN, quinacrine (0.1 micromol/L), blocked this action. CpG-ODN reduced the rate of senescence and cell death of monocytes in culture but did not influence their phagocytosis, procoagulant activity, or support of the mixed lymphocyte response. Four days of exposure of monocytes to CpG-ODN up-regulated the expression of the endotoxin receptor CD14 and down-regulated the mannose (scavenger) receptor, a result that is consistent with blocking the maturation of monocytes to macrophages. Incubation of peripheral blood monocytes (PBMCs) with CpG-ODN resulted in the generation of a heat labile factor that inhibited macrophage differentiation and accounts for the efficacy of the CpG-ODN. T cells selected from PBMCs by magnetic beads generated the majority of this factor. Cytokines (interleukin-3 (IL-3), IL-4, IL-6, IL-10, interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1) did not inhibit macrophage adherence like CpG-ODN did. Antibodies to IL-6 or IL-10 did not block the activity of CpG-ODN. Dexamethasone inhibited macrophage adherence, and lipopolysaccharide had a minor effect. We conclude that immunostimulatory CpG-ODNs inhibit macrophage adherence by provoking the production of an unidentified heat-labile factor.
 ...
PMID:Immunostimulatory CpG-oligodeoxynucleotides induce a factor that inhibits macrophage adhesion. 1056 Sep 44

A number of pathogenic and proinflammatory stimuli, and the transforming growth factor-beta (TGF-beta) exert opposing activities in cellular and immune responses. Here we show that the RelA subunit of nuclear factor kappaB (NF-kappaB/RelA) is necessary for the inhibition of TGF-beta-induced phosphorylation, nuclear translocation, and DNA binding of SMAD signaling complexes by tumor necrosis factor-alpha (TNF-alpha). The antagonism is mediated through up-regulation of Smad7 synthesis and induction of stable associations between ligand-activated TGF-beta receptors and inhibitory Smad7. Down-regulation of endogenous Smad7 by expression of antisense mRNA releases TGF-beta/SMAD-induced transcriptional responses from suppression by cytokine-activated NF-kappaB/RelA. Following stimulation with bacterial lipopolysaccharide (LPS), or the proinflammatory cytokines TNF-alpha and interleukin-1beta (IL-1beta, NF-kappaB/RelA induces Smad7 synthesis through activation of Smad7 gene transcription. These results suggest a mechanism of suppression of TGF-beta/SMAD signaling by opposing stimuli mediated through the activation of inhibitory Smad7 by NF-kappaB/RelA.
 ...
PMID:A mechanism of suppression of TGF-beta/SMAD signaling by NF-kappa B/RelA. 1065 73

Stimulation of monocytes/macrophages with lipopolysaccharide (LPS) results in activation of nuclear factor-kappaB (NF-kappaB), which plays crucial roles in regulating expression of many genes involved in the subsequent inflammatory responses. Here, we investigated roles of transforming growth factor-beta activated kinase 1 (TGF-TAK1), a mitogen-activated protein kinase kinase kinase (MAPKKK), in the LPS-induced signaling cascade. A kinase-negative mutant of TAK1 inhibited the LPS-induced NF-kappaB activation both in a macrophage-like cell line, RAW 264.7, and in human embryonic kidney 293 cells expressing toll-like receptor 2 or 4. Furthermore, we demonstrated that endogenous TAK1 is phosphorylated upon simulation of RAW 264.7 cells with LPS. These results indicate that TAK1 functions as a critical mediator in the LPS-induced signaling pathway.
 ...
PMID:TAK1 mediates an activation signal from toll-like receptor(s) to nuclear factor-kappaB in lipopolysaccharide-stimulated macrophages. 1067 30

The endothelin-1 (ET-1) concentrations were measured by RIA in the media of confluent monolayer cultures of rat articular chondrocyte (RAC) exposed to fetal calf serum (FCS) and several growth factors and cytokines. The cells were obtained from 1- and 18-month-old rats. First passage cells were starved in Dulbecco's modified Eagle's medium (DMEM) containing 0.2% FCS serum for 24 h and then incubated for 48 h in the same fresh medium with each of the following factors: fetal calf serum (FCS), transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), and NO donor, sodium nitroprusside (SNP). The following was found: the cells from 18-month-old animals accumulated about twice as much ET-1 per microg DNA under basal (low serum) and stimulated conditions as cells from young rats. All, but PDGF and SNP produced concentration-dependent rise in ET-1 levels, the most effective being 10% FCS, IL-1beta, TNF-alpha, EGF, IGF-1 and LPS. TGF-beta caused the smallest stimulation and PDGF was ineffective or slightly inhibitory at high concentrations. SNP caused concentration-dependent decrease of ET-1 concentrations. ET-1-specific mRNA was identified by RT-PCR in cells incubated with the above factors and its concentration paralleled that of the peptide. This suggests that ET-1 found in the culture media of RAC stems, at least in part, from the synthesis. Increased immunoreactive peptide concentration and mRNA expression with the age of the donor rat and its regulation by several growth factors and cytokines suggest the involvement of ET-1 in chondrocytes' physiology and possibly pathology.
 ...
PMID:Endothelin-1 in monolayer cultures of articular chondrocytes from young and old rats: regulation by growth factors and cytokines. 1073 80

The lack of cell lines from mononuclear phagocytes of salmonid fish has impeded the study of immune function at a cellular level in these economically and ecologically important animals. Here, we report on the further characterization of RTS11, a previously described macrophage-like cell line from the rainbow trout spleen, with regard to its expression of a number of immunologically relevant genes. Analysis of gene expression by reverse transcription-polymerase chain reaction, using rainbow-trout-specific primers demonstrated that RTS11 cells express the beta chain of the class II major histocompatibility complex, the cytokines transforming growth factor-beta (TGF-beta) and interleukin-1beta (IL-1beta), and cyclo-oxygenase-2 (COX-2). Inducing the cells with lipopolysaccharide led to increased expression of IL-1beta and COX-2, as determined by Northern blotting. These results together suggest that RTS11 retains many of the characteristics expected of mature macrophages, and should be a valuable tool for further study of the expression and function of these immunomodulatory proteins in fish.
 ...
PMID:Constitutive and LPS-induced gene expression in a macrophage-like cell line from the rainbow trout (Oncorhynchus mykiss). 1083 91

Endotoxin tolerance (ET) has been described as a temporary alteration in the lipopolysaccharide (LPS) response of monocytic cells after an initial LPS exposure with respect to the production of soluble immunomodulators. Apart from the LPS response, monocytic cells play an important role in initiation of the specific immune response as antigen-presenting cells. This study investigated the capacity of human blood monocytes to induce T-cell stimulation in ET. First, the expression of monocyte surface molecules, important for T-cell interaction, was analyzed by flow cytometry. In vitro priming of peripheral blood mononuclear cells with LPS clearly down-regulates major histocompatibility complex class II molecules and the costimulatory molecule CD86. Both changes were dependent on the endogenous interleukin (IL)-10 and less so on the transforming growth factor-beta. In contrast, other accessory molecules on monocytes were only marginally down-regulated (CD58), were not significantly changed during ET (CD40), or even remained up-regulated after initial LPS priming (CD54, CD80). Second, an impact of these phenotypic alterations on the accessory function of monocytes was observed. This was manifested as diminished T-cell proliferation and interferon (IFN)-gamma release in response to the presence of different recall antigens. Neutralizing IL-10 during LPS priming prevented the diminished T-cell IFN-gamma production but had little effect on T-cell proliferation. These data confirm that ET is an appropriate model of the monocyte functional state in immunoparalysis, which is frequently observed in patients after septic shock, trauma, or major surgery.
 ...
PMID:Impaired antigen presentation by human monocytes during endotoxin tolerance. 1089 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>