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)

The new quinoline derivative antibiotics (quinolones), pefloxacin and ciprofloxacin at concentrations higher than 50 micrograms/ml inhibit the PHA response of the human mononuclear leukocytes in vitro. Since monocytes have been shown to be accessory cells for the activation of lymphocytes by mitogens, we investigated the effects of pefloxacin and ciprofloxacin on extracellular interleukin 1 (IL-1) and cell-associated IL-1 from lipopolysaccharide-stimulated human monocytes. Pefloxacin and ciprofloxacin decreased the extracellular IL-1 in a dose-dependent manner, while cell-associated IL-1 was not altered. These effects were observed even after a short period of incubation (1 or 2 h). No inhibitory activity against purified IL-1 or IL-2 could be demonstrated in the dialyzed supernatants from pefloxacin- or ciprofloxacin-treated monocytes. Neither pefloxacin nor ciprofloxacin modified the biological activity of preformed IL-1. The decrease of extracellular IL-1 induced by pefloxacin and ciprofloxacin could, in part, account for the observed decrease in the proliferative response of human mononuclear leukocytes to phytohemagglutinin, as extracellular IL-1 and proliferative response were positively correlated (at various concentrations of pefloxacin and ciprofloxacin). The decrease in extracellular IL-1 was not associated with any alteration in the expression of the HLA-DR antigen on the monocytes membrane. These data suggested that pefloxacin and ciprofloxacin could antagonize IL-1 production and release by lipopolysaccharide-stimulated monocytes. These quinolones could be interesting tools to study the production, processing, transport and release from the monocytes of IL-1.
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PMID:Effects of quinolones on interleukin 1 production in vitro by human monocytes. 349 23

Augmented IgE production and increased infections are often seen in allergic patients. As monocytes (MN) and polymorphonuclear leukocytes (PMN) are involved in both immune regulation and inflammatory reaction, MN function in terms of monokine production stimulated with lipopolysaccharide (MN supernatant; MN-sup) and its biological activity and the response of PMN to MN-sup and recombinant interleukin-1 (rIL-1) regarding chemotactic activity and expression of IgG Fc receptor (FcR) were studied in 26 normal children and 28 new and 22 hyposensitized (HS) asthmatic children. The results showed the following. There was no difference in IL-1 production, as assayed by thymocyte proliferation, among the three groups. All MN-sup from the three groups could enhance IL-2 production, but that of new patients was less efficient. In the absence of PWM, MN-sup of new patients greatly augmented the production of IgG, IgA, IgM, and IgE, but that of HS patients could enhance only IgE synthesis. MN-sup of patients enhanced less efficiently the chemotactic activity and FcR expression of PMN from healthy volunteers, and PMN from asthmatics responded much less vigorously to rIL-1 regarding the above-mentioned functions. The number of PMN with membrane IL-1 was much lower in allergic patients. Thus the abnormal MN and PMN functions may be used to explain partly the augmented IgE production and increased infections in allergic patients.
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PMID:Defective monokine production and decreased responsiveness of polymorphonuclear leukocytes to recombinant interleukin-1 in asthmatic patients. 349 52

Considerable evidence suggests that the high frequency of B cells committed to the IgA isotype in Peyer's patches is regulated by T lymphocytes. To understand more accurately the mechanism of this immunoregulation, an autoreactive T cell line from Peyer's patches was generated by culturing L3T4+ Peyer's patches T cells with syngeneic B cell blasts. The resulting T cell line, designated PT-1, and a clone derived from this line, PT-1.14, stimulated immunoglobulin secretion in spleen B cells with a preferential enhancement of IgA and IgG1 isotypes. Supernatant derived from concanavalin A-stimulated PT-1 or PT-1.14 cells could also enhance IgA secretion if spleen B cells were preactivated with lipopolysaccharide. Peyer's patches T cell supernatant did not contain IgA-specific binding factors. PT-1 supernatant scored positive in lymphokine assays for interleukin (IL)-2, IL-4 (B cell stimulatory factor 1), IL-5 (B cell growth factor II), and interferon-gamma, whereas PT-1.14 supernatant was positive for IL-4 and IL-5 and negative for IL-2 and interferon-gamma. Only IL-5 enhanced IgA secretion in lipopolysaccharide-activated B cells and this response was increased two- to three-fold by IL-4. These results suggest that the type 2 T helper subset which produces both IL-5 and IL-4 plays a primary role in regulating IgA expression.
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PMID:Interleukin 5 and interleukin 4 produced by Peyer's patch T cells selectively enhance immunoglobulin A expression. 349 68

Male Fischer-344 rats at 5, 11, and 18 months of age were exposed to chronic stress for 6 months and subsequently allowed a 1-month interval with no stress before examination of splenic lymphocyte proliferative responses, IL-2 secretion by T cells, and NK cell activity in stressed and age- and sex-matched control animals. All four responses declined as a function of age in control rats. Stress exposure significantly decreased concanavalin A and lipopolysaccharide proliferative responses in 12- and 18-month-old compared to control rats without altering IL-2 secretory capacity. NK cell activity was slightly depressed by stress only in 18-month-old rats. By contrast, in 25-month-old animals that already demonstrated immune response levels lower than those of younger animals, stress did not significantly affect the responses examined. Thus, younger rats were more susceptible to a decline in host-defense responses induced by long-term chronic stress than older rats. Overall, the data suggest that aging significantly and differentially modulates the ability of environmental stress to influence the immunocompetent status of the organism.
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PMID:Effects on immune responses by chronic stress are modulated by aging. 350 11

Spleen cells from C57BL/6 beige mouse showed significantly lower cytotoxic T lymphocyte (CTL) generation in vitro against allogeneic target cells as compared with spleen cells from the wild type, whereas the heterozygous littermate showed a response similar to that of the wild type. In contrast, the responsiveness of beige spleen cells in the mixed lymphocyte reaction against allogeneic stimulator cells was in the normal range, suggesting that beige spleen cells recognize allogeneic stimulator cells to the same extent as spleen cells from normal mouse, resulting in a significant proliferation. The addition of interleukin 1 (IL-1)-containing supernatant from lipopolysaccharide-stimulated J774.1 cells to the culture of spleen cells from beige mouse stimulated with allogeneic cells restored the impaired CTL generation in a dose-dependent manner. The molecules responsible for restoration of the impaired CTL response co-migrated with IL-1 on gel filtration. The addition of purified interleukin 2(IL-2) also augmented the induction of CTL from beige spleen cells. However, the magnitude of augmentation by IL-2 was appreciably lower than that of augmentation by IL-1. These results suggest that the role of IL-1 in the induction of CTL is not only to provide a signal for activated amplifier T cells to release IL-2, but also to magnify otherwise low responsiveness of CTL-precursors and/or CTL-helpers. Moreover, intraperitoneal injection of IL-1 without allo-antigenic stimulation was able to restore the in vitro CTL responsitivity to allo-antigen but not the natural killer cell activity, indicating that IL-1 has a therapeutic potential in vivo for preferentially correcting impaired CTL generation associated with beige mutation.
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PMID:Interleukin-1 restores the impaired cytotoxic T lymphocyte generation in beige mutant mouse. 623 64

Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals.
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PMID:Lymphoid abnormalities in rats with adjuvant-induced arthritis. I. Mitogen responsiveness and lymphokine synthesis. 633 88

Culture supernatants (CS) from Hodgkin derived cell lines have previously been shown to contain colony stimulating activity (CSF) for human cord blood cells, fetal bone marrow and fetal liver cells. In this study 3-day CS from four Hodgkin lines (L428, L538, L540, L591) and two sublines (L428KS, L428KSA) were examined for interleukin (IL) activity. None of the tested CS supported the growth of an IL-2 dependent murine T-cell line, suggesting that the Hodgkin lines do not produce significant amounts of IL-2. When crude 3-day CS from the various lines were assayed for IL-1-activity in the conventional murine thymocyte costimulator assay no or only borderline IL-1-activity was detectable. However, concentrated CS from L428KS exhibited IL-1-activity also in this assay as did lipopolysaccharide (LPS) induced human IL-1. Surprisingly, crude 3-day CS from all Hodgkin cell lines were capable of fully replacing the accessory cell requirement in ConA-induced lymphoproliferation assays of heavily monocyte-depleted human blood lymphocytes. The monocyte-depleted lymphocyte populations were obtained by 1 X g sedimentation at a sedimentation rate of 30.2 to 38.8 mm/hr (fraction IIIa and IIIb). These cells responded poorly to the T-cell mitogen ConA at 10 micrograms/ml and produced no IL-2. Addition of irradiated, autologous monocytes or of CS from the various Hodgkin cell lines quantitatively restored the ConA responsiveness and induced significant IL-2 production in the monocyte-depleted lymphocyte population, suggesting that Hodgkin lines constitutively secrete IL-1 or IL-1-like activity. A preliminary biochemical characterization (heat and pH stability, molecular weight range of 13-24 KD) supports the notion that the accessory cell replacing activity present in CS of Hodgkin cell lines is a type of human IL-1.
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PMID:Interleukin-1-like activity constitutively generated by Hodgkin derived cell lines. I. Measurement in a human lymphocyte co-stimulator assay. 661 Jun 30

Measurements of cytokine levels in serum may not adequately reflect the cytokine-producing potential of immune cells because of the short half-lives of cytokines and the presence of various inhibitors in human sera. In vitro cytokine production by peripheral blood mononuclear cells (PBMCs) can be an important and reliable measure of immunocompetence. Also, spontaneous in vitro release of cytokines by PBMCs may serve as a measure of their activation in vivo. In the present study, normal ranges for the in vitro production by PBMCs of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-2, and gamma interferon (IFN-gamma) were established; the feasibility of using cryopreserved PBMCs for assays of in vitro cytokine production was evaluated; and spontaneous (unstimulated) versus induced production of cytokines by fresh and cryopreserved PBMCs from healthy donors was compared. Supernatants obtained from paired fresh and frozen PBMCs were quantitated for IL-1 beta, TNF-alpha, IL-2, and IFN-gamma by using enzyme-linked immunosorbent assay or a radioimmunoassay standardized against World Health Organization cytokine standards. Fresh or cryopreserved PBMCs activated with lipopolysaccharide produced comparable levels of IL-1 beta. However, the mean levels of stimulated production of TNF-alpha, IFN-gamma, and IL-2 were significantly higher in cryopreserved versus fresh PBMCs (P < or = 0.0004). Correlations between the level of production of each cytokine by fresh versus cryopreserved in vitro-stimulated PBMCs were statistically significant, although of moderate magnitude. Spontaneous cytokine release by fresh versus cryopreserved cells was not significantly different.
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PMID:In vitro cytokine production by normal human peripheral blood mononuclear cells as a measure of immunocompetence or the state of activation. 749 60

In the immune system macrophages are the cells responsible for nitric oxide (NO) production. The synthesis of NO by activated macrophages correlates with their cytotoxic effect on neoplastic cells as well as killing of intracellular parasites. In the present paper we test several parameters that may influence (in vitro) NO production by murine peritoneal macrophages previously stimulated in vivo by intraperitoneal injection of thioglycollate. In our system the maximum NO/NO2- release was obtained in the culture containing 10(6) M phi/ml after 24 h incubation. For macrophage activation we used lipopolysaccharide (LPS) and several recombinant cytokines (IFN-gamma, TNF-alpha, IL-2, IL-3, IL-6). We also tested the influence of latex phagocytosis on NO production by simultaneously activated macrophages.
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PMID:An improved experimental model for the study of in vitro release of nitric oxide by murine peritoneal macrophages. 750 53

Recent demonstration of cytokine-inducible production of nitric oxide (NO) in vascular smooth muscle cells (VSMC) from rat aorta has implicated VSMC-derived NO as a key mediator of hypotension in septic shock. Our studies to determine whether an inducible NO pathway exists in human VSMC have revealed a novel cytokine-inducible, NO-independent pathway of guanylate cyclase activation in VSMC from human saphenous vein (HSVSMC). Interleukin 1 (IL-1), tumor necrosis factor (TNF), interferon gamma (IFN-gamma) and Escherichia coli lipopolysaccharide (LPS) increased cGMP at 24 h, whereas IL-2 and IL-6 were ineffective. The effect of IL-1 on cyclic guanosine 3',5'-monophosphate (cGMP) was delayed, occurring after 6 h of exposure, and was maximal after 10 h. Methylene blue and LY83583 reversed the IL-1-induced increase in cGMP, suggesting that it was mediated by activation of soluble guanylate cyclase. However, IL-1-induced cGMP in HSVSMC was not inhibited by extracellular hemoglobin. Also, the effect of IL-1 on cGMP was not reversed by nitro- or methyl-substituted L-arginine analogs, aminoguanidine, or diphenyleneiodonium, all of which inhibit IL-1-induced NO synthase in rat aortic VSMC (RAVSMC). IL-1-induced cGMP in HSVSMC was also independent of tetrahydrobiopterin and extracellular L-arginine, as it was not affected by 2,4-diamino-6-hydroxyprytimidine, an inhibitor of tetrahydrobiopterin biosynthesis, and was similar in L-arginine-free and L-arginine-containing media. Analysis of NO synthase mRNA with the use of polymerase chain reaction indicates that levels of mRNA for inducible NO synthase are several orders of magnitude lower in IL-1-treated human HSVSMC than in IL-1-treated RAVSMC. IL-1-induced cGMP was also NO independent in human umbilical artery VSMC, and NO dependent in rat vena cava VSMC. Together these results indicate that IL-1 activates a novel NO-independent pathway of soluble guanylate cyclase activation in human VSMC.
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PMID:Interleukin 1 activates soluble guanylate cyclase in human vascular smooth muscle cells through a novel nitric oxide-independent pathway. 750 3


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