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

Interferon-gamma is a critical factor in the activation of several mononuclear phagocyte effector and immunoregulatory properties. However, it remains uncertain if IFN-gamma is capable of concurrent activation of both functions in the same cell population. Plastic adherent mononuclear cells (80-98% MN by cytochemical criteria) were cultivated in the absence or presence of recombinant interferon-gamma (rIFN-gamma, 0.1-100 U/ml) for 48 hr. MN surface DR antigen was assessed by flow cytometry (EPICS V) after staining with monoclonal antibodies OKIa1 or L243. Exposure to rIFN-gamma (100 U/ml) increased MN surface DR antigen (mean fluorescence intensity) by 80 +/- 20% (P less than 0.01) and 121 +/- 52% (P less than 0.001), respectively, compared to untreated cells. The increase in DR antigen was maximal at 100 U/ml, dependent on protein and RNA synthesis and blocked by agents that increase cAMP levels. IL-1 activity was determined in the mouse thymocyte assay; rIFN-gamma (100 U/ml) increased IL-1 activity in the supernatants of MN cultured in medium alone from 0.5 +/- 0.2 to 7.8 +/- 4.7 U/ml (P less than 0.05), and lipopolysaccharide-stimulated MN from 20.4 +/- 19.1 to 71.7 +/- 38.9 U/ml (P less than 0.05). Following rIFN-gamma exposure, MN stimulation of the AMLR was increased at 6 days (29,269 +/- 5224 vs 13,252 +/- 4938 cpm, P less than 0.01). Spontaneous cytotoxicity (SC) and antibody-dependent cell cytotoxicity (ADCC) were studied in a 51Cr release microculture assay using the human lymphoblastoid cell line CCRF-CEM as target. SC by MN increased linearly as a function of log[rIFN-gamma] for effector:target (E:T) ratios of 5:1 (r = 0.95, P less than 0.01) and 10:1 (r = 0.99, P less than 0.01). ADCC by MN increased following rIFN-gamma exposure (100 U/ml) at E:T ratios of 5:1 (22 +/- 13 to 31 +/- 4%, P less than 0.025) and 10:1 (31 +/- 4 to 38 +/- 4%, P less than 0.01). Thus, rIFN-gamma not only activates MN effector function, but has concurrent stimulatory effects on multiple MN properties critical to immunoregulation.
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PMID:Concurrent enhancement of monocyte immunoregulatory properties and effector functions by recombinant interferon-gamma. 294 10

We have used the RAW 264.7 macrophage (MO) cell line to study cAMPdPK isozymes during activation by lymphokine (LK) and lipopolysaccharide (LPS). Untreated cells were found to have two isozymes of cAMPdPK in their cytosol. PKI and PKII were differentiated based on the Mr of their regulatory subunits (RI, 45,500; and RII, 52,000, respectively) as determined by photoactivated incorporation of the cAMP analog 8-N3-[32P]cAMP. Loss of the RI subunit of PKI occurred in association with activation of the cell line by suboptimal concentrations of LK and LPS (1/40 dilution, 1 ng/ml) or high concentrations of LPS alone (10 ng/ml to 100 micrograms/ml). No modulation of the RII subunit of PKII was observed under these conditions. The loss of RI was dependent on the addition of a triggering signal to the MO. Treatment of RAW 264.7 cells with LK alone at dilutions from 1/10 to 1/1280 was not sufficient to cause a disappearance of the RI subunit from the cytosol or to induce antitumor activity. The addition of a suboptimal concentration of LPS after LK or a high dose of LPS alone was required for acquisition of cytolytic activity and loss of RI. The kinetics for the disappearance of RI from treated cells were found to be identical after activation with either LK and LPS or high concentrations of LPS alone. RI could no longer be detected in the cytosol 8 hr after the addition of activating agents. The antitumor activity of the RAW 264.7 cell line was transiently expressed after activation. Cells no longer exhibited tumoricidal activity 48 hr after the removal of activating agents. It was observed that the loss of cytolytic function was accompanied by the reexpression of RI in the cytosol. This study provides evidence that modulation of cAMPdPK isozymes occurs during activation, suggesting a potential mechanism for controlling the effects of cAMP on the MO.
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PMID:Modulation of cyclic AMP-dependent protein kinase isozyme expression associated with activation of a macrophage cell line. 299 44

Prior exposure of guinea pig macrophages to LPS (lipopolysaccharide) resulted in reduced cAMP-generating responses to prostaglandin E1 and epinephrine. LPS-induced refractoriness was diminished when LPS treatment was carried out in the presence of an inhibitor of prostaglandin synthesis, hydrocortisone, or indomethacin, or an inhibitor of protein synthesis, cycloheximide. The release of arachidonic acid and its metabolites, especially prostaglandin E2 and thromboxane B2, increased during incubation of macrophages with LPS. These increases were efficiently antagonized by hydrocortisone, indomethacin, or cycloheximide. Preincubation of macrophages with prostaglandin E1 greatly reduced the subsequent responses of cAMP generation to prostaglandin E1 and unexpectedly also to epinephrine. Thus, increased production of prostaglandins during the LPS treatment is likely to be responsible for decreased cAMP responses to subsequent addition of prostaglandin E1 and epinephrine.
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PMID:Induction of refractoriness of cyclic AMP responses to prostaglandin E1 and epinephrine by prior exposure of guinea pig macrophages to lipopolysaccharide. 301 Aug 70

Macrophages, which produce the collagenolytic enzyme collagenase, are commonly found at sites of connective tissue destruction in chronic inflammatory lesions. Since tissue macrophages are derived from circulating peripheral blood monocytes, we used these less-differentiated, more readily available cells to examine the production and regulation of collagenase. Human monocytes, isolated in large quantities by counterflow centrifugal elutriation, were shown to produce substantial amounts of collagenase when stimulated by concanavalin A (Con A) and to a lesser extent with lipopolysaccharide, while unstimulated monocyte cultures produced negligible collagenase. Collagenase was detected in the culture media within the first 24 hr of culture after activation with peak production at 48 hr. Analysis of the intracellular regulation of collagenase revealed that synthesis of this enzyme required a prostaglandin (PGE2)-dependent step since indomethacin-inhibited enzyme synthesis was reversed by PGE2. Additionally, dibutyryladenosine cyclic monophosphate (dBcAMP) restored collagenase synthesis in indomethacin-blocked cultures, indicating a PGE2-dependent generation of cAMP requirement for collagenase production similar to that demonstrated in experimental animals systems. In additional studies, anti-inflammatory drugs which are known to modulate connective tissue destruction were analyzed for their influence on monocyte-derived collagenase. Dexamethasone, colchicine or retinoic acid all inhibited collagenase synthesis by monocytes in a dose-dependent manner although the effect of these drugs on monocyte PGE2 synthesis differed. Dexamethasone inhibited PGE2 synthesis, which resulted in the suppression of collagenase. However, PGE2 production was unaffected by colchicine whereas retinoic acid caused a significant increase in PGE2 levels. Inhibition of collagenase synthesis by dexamethasone, but not colchicine or retinoic acid, could be reversed by PGE2 or phospholipase A2. These findings provide insight into the intracellular events regulating monocyte collagenase synthesis and also implicate monocytes as a target of anti-inflammatory agents which ameliorate connective tissue degradation associated with chronic inflammatory lesions.
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PMID:Regulation of human peripheral blood monocyte collagenase by prostaglandins and anti-inflammatory drugs. 303 63

The biochemical events leading to enhanced membrane expression of HLA-DR and CR3 by human peripheral blood monocytes (MO) following exposure to bacterial lipopolysaccharide (LPS) were examined. In a previous study we demonstrated that an increase in intracellular calcium was necessary, but not sufficient, for MO to increase membrane expression of both antigens within 1 hr of addition of LPS. The present study was initiated to examine the other biochemical requirements which lead to the MO response to LPS. Enhanced expression of both antigens following addition of LPS was dependent on microfilament function, but independent of microtubule function and of protein synthesis. Inhibition of formation of cyclooxygenase or lipoxygenase metabolites of arachidonic acid had no effect on HLA-DR or CR3 modulation by LPS. A role for phosphatidylinositol metabolism was suggested by the inhibition of the MO response to LPS by dibutyryl cAMP and theophylline and by the enhanced expression of both antigens following addition of phorbol diesters. However, H-7, a putative inhibitor of protein kinase C, did not alter the MO response to LPS or phorbol diesters. These results suggest that LPS enhances expression of HLA-DR and CR3 by inducing redistribution of these antigens from an intracellular pool. The data also support a role for the generation of hydrolysis products of phosphatidylinositol, leading to calcium redistribution and activation of protein kinase C or other kinases, in the MO response to LPS.
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PMID:Biochemical basis of HLA-DR and CR3 modulation on human peripheral blood monocytes by lipopolysaccharide. 303 40

Stimulant action of the mitogenic polyanion, polyacrylic acid (PAA) was investigated in mouse lymphocyte culture in vitro. B cell division was induced by "impulsive" PAA treatment. Shortly after PAA treatment the activity of the membrane enzymes, adenylate and guanylate cyclases, was assayed according to the changes in the concentration of cAMP and cGMP. The effect of PAA on the time course of cAMP and cGMP in lymphocytes was compared to the effect of B cell mitogen of other chemical nature--bacterial lipopolysaccharide (LPS). PAA was demonstrated to produce no effect on the activity of membrane cyclase enzymes. On the contrary, following LPS addition guanylate cyclase in the lymphocyte membrane was activated within the first 5-10 minutes. Later on (after 2h) the cells activated with LPS showed an increase in adenylate cyclase activity. By the 12th-24th hour the concentration of cAMP in the LPS-stimulated cells reached 250% of the control level. The differences are discussed between the mitogenic polyanion (PAA) and the lipid-modifying mitogen (LPS) in the molecular mechanisms by which the lymphocyte responses are activated.
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PMID:[Analysis of the cyclase enzyme activity of the cell membrane following lymphocyte stimulation with a mitogenic polyanion]. 614 37

A protein resembling calmodulin was isolated from non-parenchymal and parenchymal cells of rat liver by affinity chromatography. The biological activity of the purified protein was assessed by the bovine brain cAMP phosphodiesterase assay. A highly sensitive radioimmunoassay as well as the cAMP phosphodiesterase method were employed to determine the calmodulin content of crude extracts from monolayer cultures of rat Kupffer cells and hepatocytes. An ATP-dependent, calmodulin-enhanced calcium transport was demonstrated in a membrane fraction of the non-parenchymal cells. Phospholipase A2 activity specific for 2-arachidonoyl phosphatide and with a pH optimum of 8.1 was measured in homogenized Kupffer cells; it was stimulated by agents previously shown to enhance prostaglandin synthesis in Kupffer cells, e.g. zymosan particles and lipopolysaccharide isolated from Salmonella minnesota. The increase in activity was completely prevented by pretreatment with or simultaneous addition of R 24571, a known calmodulin antagonist. However, if this inhibitor or calmodulin was added to the cell-free extract phospholipase A2 activity was not influenced. Phospholipase A1 activity could be detected at pH 5 only, showing a slight decrease in the homogenate of stimulated macrophages. Acyltransferase activity was high but independent of treatment of the Kupffer cells.
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PMID:Calmodulin content and activity of Ca2+-ATPase and phospholipase A2 in rat Kupffer cells. 623 Nov 83

The production of collagenase by lipopolysaccharide-(LPS) activated guinea pig macrophages is mediated by prostaglandins (PG) of the E series. After stimulation of guinea pig macrophages with LPS, extracellular PGE levels and cellular cAMP levels are elevated. Indomethacin inhibits not only PG synthesis, but also cAMP and collagenase production in LPS-stimulated macrophage cultures. In these indomethacin-inhibited cultures containing LPS, dibutyryl (dB) cAMP, or cholera toxin can restore macrophage collagenase production but not PG synthesis. Moreover, dBcAMP and cholera toxin enhance collagenase production in LPS-activated cultures. Initial activation of the macrophages by an agent such as LPS is a prerequisite for synthesis of collagenase, since in the absence of LPS, dBcAMP or cholera toxin alone are ineffective stimuli. These findings clearly demonstrate a role for PG-induced elevations of cAMP in the production of collagenase by LPS-activated macrophages.
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PMID:Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate. 624 42

The level of cAMP in macrophages, intestinal mucosa and blood plasma as well as its formation in intestinal mucosa of germfree animals under the effect of lipopolysaccharide E. coli 055 (LPS) were studied in experiments on germfree and ordinary mice and guinea-pigs. The concentration of cAMP in intestinal mucosa of ordinary guinea-pigs was 5-fold higher than in germfree animals. LPS induced an increase in cAMP level in intestinal mucosa, but this level did not reach that in ordinary animals. The levels of cAMP in blood plasma of germfree guinea-pigs in macrophages of germfree mice increased 2-fold and 4-fold, respectively, 30 minutes following the treatment with LPS. The increased level of cAMP was accompanied by its intensive secretion into the exocellular medium. Macrophages of ordinary animals had a moderate output of cAMP. A conclusion is made about the relationship between cAMP formation and microbial contamination of the microorganism as well as about an important role of the cyclic nucleotide in the mechanism of nonspecific resistance and homeostatic reactions of the body to microbial exposure.
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PMID:[Cyclic 3',5'-adenosine monophosphate in macrophages, intestinal mucosa, and blood plasma of germ-free and ordinary animals]. 625 Jun 53

Kupffer cells exposed to bacterial lipopolysaccharide in vitro synthesized collagenase and released the major portion of it into the extracellular space while the intracellular level of enzyme was not altered significantly. Cycloheximide prevented the appearance of collagenase in the medium indicating de novo synthesis. Indomethacin, an inhibitor of cyclooxygenase, also blocked collagenase synthesis. In line with this observation. Kupffer cells were found to synthesize substantial amounts of prostaglandin E2 when exposed to lipopolysaccharide; concomitantly, cellular cAMP levels were increased. Indomethacin was shown to abolish the stimulated cAMP formation. Addition to the culture medium of cAMP or dibutyryladenosine 3', 5'-monophosphate as well as of prostaglandin E2 or, to a lesser extent, prostaglandin E1 allowed indomethacin-inhibited cells to resume the production of collagenase. It is proposed that in rat Kupffer cells lipopolysaccharide-elicited collagenase synthesis and excretion is mediated sequentially by stimulated production of prostaglandin E2, enhanced adenylate cyclase activity and increased intracellular cAMP levels.
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PMID:Involvement of prostaglandin E and adenosine 3', 5'-monophosphate in lipopolysaccharide-stimulated collagenase release by rat Kupffer cells. 628 7


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