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)

Tumor necrosis factor-alpha (TNF-alpha), a product of both mononuclear phagocytes and T lymphocytes, is an important proximal mediator of a number of acute and chronic inflammatory disease states. In this investigation we examine the regulatory effects of the lymphocyte product interleukin-4 (IL-4) on the gene expression of TNF-alpha from stimulated human peripheral blood monocytes (PBM) and T lymphocytes. We demonstrated the dose-dependent suppression of TNF-alpha mRNA and protein synthesis from lipopolysaccharide-treated PBM by IL-4. The suppressive effects of IL-4 appear to be dependent upon de novo protein synthesis, as cycloheximide abrogated the IL-4-induced reduction in TNF-alpha mRNA levels from PBM. In contrast to the suppressive effects of IL-4 on PBM-derived cytokine expression, IL-4 did not alter TNF-alpha mRNA expression from alpha-Cd3 or PMA + alpha-CD-28-treated T lymphocytes. Moreover, IL-2 mRNA expression from similarly treated T lymphocytes was unaltered by IL-4. Our findings demonstrate that disparity exists in the regulation of TNF-alpha gene expression from different immune cell populations which may have important implications in the evolution of acute and chronic inflammatory responses.
 ...
PMID:Interleukin-4 differentially regulates tumor necrosis factor-alpha gene expression by human T lymphocytes and monocytes. 157 Oct 90

We investigated the relationship of polymorphonuclear leukocyte (PMN) candicidal activity, matrix proteins, and lipopolysaccharide (LPS) to determine how LPS modulates the normal enhancing effect of matrix proteins on PMN candicidal activity. LPS reduced PMN candicidal activity when PMN were adhered in the presence of either fibronectin or laminin. In the presence of fibronectin or laminin, LPS reduced CD11b/CD18 expression (the fibronectin receptor) as assessed using sheep erythrocytes coated with C3bi. Experiments with 125I-fibronectin and 125I-RGDS (Arg-Gly-Asp-Ser) demonstrated that LPS reduced both the binding of fibronectin and the bioavailability of the binding epitope on the PMN surface. Stimulating the PMN oxidative burst with PMA but not FMLP also reduced fibronectin and RGDS binding. Incubation of LPS-treated PMN with staurosporine blocked the decrease in fibronectin and RGDS binding. Exposure of PMN to LPS plus low-dose TNF-alpha restored both fibronectin and RGDS binding with a concomitant increase in CD11b/CD18 surface expression. Low-dose TNF-alpha restored PMN candicidal activity in the presence of LPS and was most effective if PMN were preadhered to fibronectin. These results demonstrate that: (1) matrix proteins enhance normal PMN candicidal activity, (2) LPS reduces PMN candicidal activity in the presence of matrix proteins, (3) stimulation of the PMN oxidative burst in particular via protein kinase c activation reduces the bioavailability of the fibronectin receptor, and (4) low-dose TNF-alpha may restore PMN candicidal activity in part by upregulating the surface receptor for fibronectin binding.
 ...
PMID:Endotoxin suppresses matrix protein-induced upregulation of PMN candicidal activity: an effect reversed by low-dose TNF-alpha. 161 18

There are relatively few monoclonal antibodies (MAbs) to rat monocyte/macrophages available. We describe here 2 new such antibodies. The first, 109.2, recognizes most rat monocyte/macrophages and all polymorphs. The antigen recognized by this antibody is upregulated by 15 mins exposure to PMA (Phorbol myristate acetate) but down regulated by overnight exposure to LPS (lipopolysaccharide). It is probably an adhesion molecule and is likely to represent the rat equivalent of CD11b. The second antibody, 112.1, recognizes lysozyme in rat macrophages, particularly alveolar macrophages. In addition it also recognizes lysozyme in hen, rabbit and human macrophages. It also recognizes lysozyme in other tissues such as Paneth cells and proximal renal tubular cells.
 ...
PMID:Two new anti-rat macrophage monoclonal antibodies. 164 Dec 66

The requirements for activation of anti-mycobacterial and anti-listerial activity of human monocytes were investigated. Human monocytes could be activated to display enhanced anti-mycobacterial activity by a 24-h treatment with lipopolysaccharide. The mediator induced by this treatment was identified as being tumour necrosis factor-alpha (TNF-alpha). Addition of recombinant TNF-alpha (rTNF-alpha) to the cultures of human monocytes for 24 h yielded comparable results (minimal dose required for induction of anti-mycobacterial activity, 10 U ml). Addition of anti-TNF-alpha antibody completely abrogated the effect. A similar treatment protocol failed to activate enhanced anti-listerial activity. To trigger anti-listerial activity, sequential treatment of human monocytes with rTNF-alpha and IL-2 was required. Treatment of monocytes with 10 U ml rTNF-alpha for 24 h followed by incubation in the presence of 200 U/ml of IL-2 for an additional 24 h yielded a reduction of listerial growth which was moderate but statistically significant (P less than 0.001). The activation of monocytes observed with rTNF-alpha/IL-2 treatment was (i) dependent on both cytokines; (ii) sequence dependent (i.e. when IL-2 was added prior to rTNF-alpha, no effect was observed); and (iii) absent in cells treated with one cytokine only. Enhancement of anti-listerial activity by sequential use of cytokines was not accompanied by an increase in oxidative burst, which indicated that oxidative mechanisms were not the reason for the observed Listeria monocytogenes growth restriction. Further support for this hypothesis was obtained after interferon-gamma treatment of human monocytes which led to an augmented PMA-inducible release of active oxygen radicals, but was not paralleled by growth restriction of L. monocytogenes. Our results indicate that TNF-alpha plays a crucial role in the activation of monocytes for growth restriction of intracellular microbes. Activation of human monocytes to restrict the growth of the facultative intracellular bacteria Mycobacterium avium intracellulare and L. monocytogenes, however, follows different patterns, the initial trigger in both cases being provided by TNF-alpha-induced signals.
 ...
PMID:Induction of anti-mycobacterial and anti-listerial activity of human monocytes requires different activation signals. 164 23

We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3) (0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2- release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual.
 ...
PMID:Modulation of human alveolar macrophage properties by ozone exposure in vitro. 165 83

Ethanol intoxication has been associated with bacterial pneumonia and tuberculosis. More recently, ethanol was shown to impair the capacity of pulmonary macrophages to produce superoxide anion and tumor necrosis factor (TNF). Furthermore, exposure to ethanol compromises macrophage's ability to respond to stimulation with TNF and granulocyte-macrophage colony-stimulating factor (GM-CSF), and kill an intracellular pathogen, Mycobacterium avium. Based on these previous findings, we examined whether exposure to ethanol affects superoxide anion production, synthesis of cytokines, and expression of membrane receptors to TNF on human monocyte-derived macrophages. Brief exposure to 10 or 50 micrograms/dl of ethanol significantly reduced the macrophage's response to a subsequent stimulus with phorbol ester (phorbol-12-myristate-13-acetate, PMA), and this unresponsive state lasts for approximately 6 h following removal of ethanol. When macrophages were then treated with lipopolysaccharide (LPS) in the presence of ethanol, high concentrations of TNF and GM-CSF were produced, but subsequent stimulation with LPS (second stimulus) was associated with significant impairment on synthesis and release of both TNF and GM-CSF. In addition, although ethanol had no effect on TNF binding to resting macrophages and to macrophages infected with M. avium, ethanol significantly reduced the expression of TNF receptors on interferon-gamma-stimulated macrophages. The ethanol-induced inhibition of macrophage function suggests potential mechanisms for suppression of the host's immune response and consequently increased susceptibility for infectious diseases.
 ...
PMID:Ethanol affects release of TNF and GM-CSF and membrane expression of TNF receptors by human macrophages. 166 88

Peripheral blood monocytes obtained from 8 colorectal cancer patients and 6 normal controls were incubated in vitro with interferon-r (IFN-r) in the presence of bacterial lipopolysaccharide (LPS). The cytotoxic properties of the monocyte were determined subsequent to the interaction with radiolabeled autologous, allogeneic, as well as cultured colorectal cancer cells. Monocytes from normal controls and all colorectal cancer patients were activated in vitro to become tumoricidal; monocytes lysed tumorigenic cells but not nontumorigenic cells. Activators of protein kinase C (e.g. phorbol esters, PMA) and Ca2+ ionophores (A23187) when added alone did not effect the activation state of the monocyte. Whereas, PMA and A23187 cooperatively reproduced the ability of IFN-r to prime monocytes for tumoricidal activity. In the presence of PMA, A23187, and EGTA, the addition of excessive Ca2+ was sufficient for priming, whereas the addition of excessive Mg2+ was much less efficient. Priming by IFN-r, however, was not blocked by EGTA. An efflux of Ca2+ from preloaded monocytes was significantly increased by A23187 and by IFN-r. Quin-2/AM, an intracellular chelator of Ca2+, blocked priming by IFN-r. The results suggest that priming of monocytes for tumoricidal function by IFN-r may be involved in the activation of protein kinase C and mobilization of intracellular Ca2+.
 ...
PMID:Tumoricidal activity of interferon-r activated peripheral monocytes in colorectal cancer patients. 171 83

In this in vitro study, the influence of serum-concentration, heat inactivation of the serum and the origin of the serum on the responsiveness of cultured human umbilical vein endothelial cells (HUVEC) to immunological challenges was investigated. Addition of human serum during stimulation with 1 microgram/ml bacterial lipopolysaccharide (LPS) increased endothelial cell ELAM-1 expression and interleukin (IL)-6 release five to ten-fold. Full endothelial cell responsiveness to LPS required 10 to 50% human serum and was largely abrogated after heating the serum for 30 minutes at 56 degrees C. Addition of newborn or fetal bovine serum instead of human serum, induced even higher IL-6 release and ELAM-1 expression in response to LPS, whilst heat-inactivation of these serum-batches only moderately decreased endothelial cell responses. Endothelial cell IL-6 release and ELAM-1 expression after stimulation with IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) were less influenced by heat inactivation of the serum and by omission of serum, whilst responses to PMA remained completely unaffected by such modifications in assay media. Finally, we demonstrated that endothelial cell IL-8 release also and ICAM-1 expression in response to LPS and cytokines were increased by addition of human serum, indicating that the use of serum-free assay media, or the use of media enriched with heat-inactivated (HI) human serum interferes with physiological endothelial cell responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:LPS and cytokine-induced endothelial cell IL-6 release and ELAM-1 expression; involvement of serum. 172 50

Studying the production of IL-6 (interleukin-6) by monocytes, endothelial cells and smooth muscle cells we observed that cytokine inducers like IL-1, TNF alpha (tumor necrosis factor alpha), LPS (lipopolysaccharide), SAC (Staphylococcus Aureus Cowan 1) and PMA could be divided roughly into two categories. Bacterial products such as LPS or SAC have a potent IL-6 inducing effect on monocytes and minor or no effect on endothelial- and smooth muscle cells. The other category comprising IL-1, TNF alpha and PMA induces IL-6 production in endothelial- and smooth muscle cells. Only IL-1 induces IL-6 production in monocytes as well as in endothelial cells and smooth muscle cells. In addition to IL-6, also IL-1 and TNF alpha are produced by monocytes however with different kinetics. None of the stimuli had any inhibitory effect on IL-6 production with the exception of PMA. Whereas PMA induced IL-6 production in endothelial cells and it potentiated the induction of IL-6 by IL-1 in these cells, it inhibited LPS-stimulated IL-6 production in monocytes. In line with the effects of PMA, staurosporin induced IL-6 production in monocytes and it inhibited IL-1 driven IL-6 production by endothelial cells.
 ...
PMID:Differential induction of interleukin-6 production in monocytes, endothelial cells and smooth muscle cells. 181 14

Polymorphonuclear leukocytes (PMN) may play a key role in acute lung injury and ARDS. The mechanisms of PMN-mediated lung injury include the release of inflammatory mediators, such as oxygen free radicals which cause direct tissue injury, and arachidonic acid metabolites which cause pulmonary vasoconstriction and increased vascular permeability. The goals of this in vitro study were 1) to assess the effects of PMN-activating agents (lipopolysaccharide, LPS; phorbol myristate acetate, PMA; tumor necrosis factor, TNF) on PMN thromboxane B2 (TXB2) release and oxygen free radical production and 2) to determine the effects of agents purported to suppress PMN activity (pentoxifylline, PTX; adenosine; dibutyryl cyclic AMP, DBcAMP; and terbutaline, TBN) on activator-induced PMN TXB2 release and oxygen free radical production. PMN TXB2 release was determined by radioimmunoassay and oxygen free radical production was monitored by chemiluminescence. Our results show that 1) LPS and PMA significantly increase PMN TXB2 release, whereas tumor necrosis factor (TNF) has no effect; 2) LPS and PMA significantly increase PMN chemiluminescence; 3) DBcAMP and TBN significantly reduce LPS-induced PMN TXB2 release whereas PTX and adenosine do not; 4) TBN significantly reduces PMA-induced PMN TXB2 release whereas other agents do not; 5) All agents (PTX, adenosine, DBcAMP, and TBN) significantly reduce LPS-induced PMN chemiluminescence but none attenuate PMA-induced PMN chemiluminescence. We conclude that: LPS and PMA activate PMN manifested by TXB2 release and chemiluminescence. Additionally, all the PMN suppressing agents do attenuate some PMN functions. Of interest, PTX, adenosine, DBcAMP, and TBN have different effects depending upon functional assay and activating agent. It will be important to investigate the mechanisms by which PMN suppressing agents alter signal transduction resulting in differential effects on PMN function.
 ...
PMID:Attenuation of LPS-induced neutrophil thromboxane b2 release and chemiluminescence. 184 34


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