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)

Carbohydrate binding proteins, known as lectins, bind to specific sugar groups on most membranes. We used fluorescent and light microscopy to study the interaction of various lectins with the membranes of microglia cultured from neonatal rat or fetal mouse cerebral cortices. Microglia stained intensely with GS-1, RCA, WGA, and ConA and slightly with DBA, UEA, BPA, and SBA. No staining was seen with GS-2, MPA, or PNA. Staining was specific for microglia in the mixed glial cultures and was dose dependent. In addition, microglial lectin binding could be reduced or blocked by competitive inhibition using specific sugars. Treatment of the microglia with agents such as dimethylsulfoxide (DMSO), interleukin-1 (IL-1), interferon (IFN), or lipopolysaccharide (LPS) did not eliminate lectin staining, although the degree of staining was altered. Positive staining of the microglia was also associated with a functional change for at least one lectin, i.e., ConA. Superoxide anion production by microglia was increased in the presence of ConA. Overall, binding of the lectins GS-1, RCA, WGA, and ConA can be used as an identifying tool for microglia in glial cultures, but intensity of staining varies depending on their functional state.
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PMID:Lectin staining of cultured CNS microglia. 137 34

The objective of the study was to examine the effect of endotoxin on early pregnancy in gilts and to test the potential of flunixin meglumine (FM), a cyclooxygenase inhibitor, to counteract abortifacient action of the endotoxin. Ten gilts at 30 days gestation were used in the experiment. Eight were injected with lipopolysaccharide (LPS) of Salmonella typhimurium, while 2 were treated with 500 micrograms cloprostenol (CP). Six of the LPS-injected gilts were treated with a total of 4 mg/kg body weight FM in 2 different dose regimens. Clinical observations were recorded and plasma levels of 15-keto-13, 14-dihydro-PGF2 alpha, progesterone and estrone sulfate (ES) were determined with radioimmunoassay. LPS induced typical signs of endotoxemia and a monophasic fever in all LPS-treated gilts. No antipyretic effect of FM was observed. The CP-treated gilts aborted within 34 h as did the gilts treated by LPS only. Of the 6 LPS + FM-treated gilts, 1 aborted within 34 h, while 5 maintained gestation. These were aborted about a week later by CP and the aborted fetuses anatomically examined. Two of the litters were lost (devoured by the dams), 2 showed no signs of earlier death and 1 showed extensive fetal death. The PGF2 alpha metabolite concentrations increased at least 10 fold immediately after the LPS injection. Progesterone plasma concentration decreased rapidly. A 5-10 fold increase in the plasma metabolite levels accompanied all abortions. CP caused no immediate change in the PGF2 alpha metabolite levels, but the abortion-related response was similar to that in LPS-injected gilts. In the FM-treated gilts, the LPS-induced PGF2 alpha metabolite response was rudimentary and the progesterone decrease temporary in nonaborting gilts. The elevated concentrations of ES decreased within 48 h in gilts aborting at 30 days gestation, while in nonaborting gilts a slow, graduate decrease of ES occurred within 3-5 days of the LPS injection. These results indicate that FM apparently suppressed LPS-induced prostaglandin synthesis and thus prevented luteolysis and abortion in early pregnant gilts.
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PMID:Endotoxin-induced abortion in early pregnant gilts and its prevention by flunixin meglumine. 208 Jul 79

Endotoxin of Gram-negative bacteria was orally administered in 5 female pigs and 8 male goats. Two of the gilts were pregnant. A solution of lipopolysaccharide (LPS) of Enterobacter agglomerans was mixed into the feed ration of the pigs (40 mg/animal), and given by gastric tube into the rumen of the goats (1-20 mg/animal). Jugular venous blood was collected and clinical signs, rectal temperature and WBC counts were recorded for 12-24 hours. Plasma concentrations of the major plasma metabolite of PGF2 alpha, 15-keto-13,14-dihydro-PGF2 alpha were determined in both species, progesterone concentration only in pigs. The pigs showed slight to severe signs of endotoxemia. Increases in rectal temperature and levels of the PGF2 alpha metabolite occurred in 3 gilts. Progesterone level and the total WBC counts remained unchanged. Differential counts followed irregular patterns mostly within the normal range. The goats showed slight signs of discomfort. Temperature increased in one animal. No other parameters were altered after the intake of LPS. The observations in pigs indicate that endotoxin either penetrated the intestinal barrier causing systemic endotoxemia or induced inflammatory reactions in the intestine activating inflammatory mediators.
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PMID:A clinical and endocrine study on the effect of orally administered bacterial endotoxin in adult pigs and goats. 211 50

When spleen cells of C57BL/6 mice were cultured, their histidine decarboxylase (HDC) activity increased with a concomitant increase in the histamine concentration in the culture medium. The addition of concanavalin A (Con A) or E. coli lipopolysaccharide (LPS) to the culture enhanced the responses. Treatment with dexamethasone or corticosterone significantly inhibited both spontaneous and Con A-dependent induction of HDC and histamine biosynthesis. Progesterone and estradiol did not inhibit but rather enhanced the responses. Testosterone had little effect on HDC activity and the histamine level of the culture medium of spleen cells. Adherent cells obtained from glycogen-stimulated peritoneal exudates had the enzyme constitutively. Con A had no appreciable effect on the HDC activity and the histamine level of the culture of these adherent cells. However, the addition of conditioned medium of T + B lymphocytes that had been incubated in the presence of Con A rendered the adherent cells responsive to Con A, leading to an increase in the HDC activity and the histamine level of the culture of the cells. Treatment with dexamethasone largely abrogated the responses. The results suggest that HDC-dependent histamine biosynthesis by peritoneal adherent cells is inhibited by glucocorticoids, which act on the adherent cells per se.
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PMID:Inhibition by glucocorticoids of mitogen-dependent histamine biosynthesis caused by histidine decarboxylase in cultured mouse spleen cells and peritoneal adherent cells. 320 36

Sex hormones have profound effects on immune responses and may influence the outcome of autoimmune diseases such as rheumatoid arthritis (RA). We investigated the effect of gonadal steroids on the production of interleukin-1 (IL-1) and IL-6, cytokines believed to be important in the pathogenesis of RA. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy male donors and male patients with RA, and were stimulated with lipopolysaccharide (LPS) in the presence of different concentrations of 17-beta-estradiol, progesterone or testosterone. In studies of cells from normal male donors, 17-beta-estradiol at pharmacological concentrations (> or = 10(-6) M) enhanced IL-1 and IL-6 secretion as well as the production of cell-associated IL-1. Progesterone and testosterone at similar concentrations inhibited IL-1 secretion but had no significant effect on IL-6 secretion or on the production of cell-associated IL-1. In studies of male RA donors, 17-beta-estradiol failed to enhance IL-1 or IL-6 secretion and progesterone failed to inhibit IL-1 secretion. The inhibitory effects of testosterone, however, appeared to be similar to that in normal donors. It is suggested that 17-beta-estradiol may promote IL-1 and IL-6 production and release, while gestation hormone, progesterone, and testosterone may inhibit IL-1 release in vivo. These data may partly explain the gender and age differences in the incidence of RA and the development of the disease in men with low and androgen levels.
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PMID:Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. 850 57

Expression and regulation of interleukin-6 (IL-6) and IL-1 beta were examined in the mouse deciduum and in experimentally induced deciduoma from 6 to 8 days postcoitum (1 dpc = vaginal plug), as well as in cultured mouse decidual cell preparations. Levels of these mRNAs in the deciduum and deciduoma were below the limits of detection by Northern blotting. However, enzymatic dispersion and culture of decidual cells and/or exposure to bacterial endotoxin-lipopolysaccharide (LPS) induced these mRNAs. IL-6 levels that accumulated in the culture medium (3990 pg/3 x 10(6) cells/day) were about 90-times higher than those of IL-1 beta (45 pg/3 x 10(6) cells/day). Progesterone (10(-7) M) modestly (40%) reduced the levels of IL-6 mRNA and protein during culture, whereas LPS dramatically (8-fold) and rapidly induced IL-6 and IL-1 beta mRNAs and proteins. In vivo, few IL-1 beta immunopositive cells were localized by immunohistochemistry in the 8 dpc deciduum. In contrast, IL-6 mRNA was localized by in situ hybridization in dispersed clusters of a few cells in the mesometrial deciduum near the center of the implantation site. LPS rapidly induced interleukin mRNAs in the deciduum and deciduoma. After LPS injection, IL-1 beta immunopositive cells were dispersed in the myometrium and mesometrial deciduum. In contrast, after LPS injection (2 h), IL-6 mRNA was abundant in 'cords' of cells that traverse the mesometrial deciduum longitudinally, as well as in cells dispersed throughout the myometrium. Thus, the IL-1 beta and IL-6 genes are expressed and regulated in distinct subsets of cells in the decidual bed. The pattern of F4/80 immunostaining is consistent with macrophages as the major, if not only, source of decidual IL-1 beta. IL-6 is also expressed in these cells. However, IL-6 gene expression is regulated in a distinct subset of cells located in the mesometrial decidual bed of the mouse.
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PMID:Regulation of interleukin-6 and interleukin-1 beta gene expression in the mouse deciduum. 892 Jan 66

The notion that stress activates central and peripheral pathways to inhibit the menstrual cycle is well accepted, but the initial processes through which this occurs have not been investigated. This study uses a relevant nonhuman primate model to document the cyclic endocrine effects imposed by a moderate short-term stress episode in the follicular phase. The stress paradigm is a 5-day inflammatory/immune-like challenge produced by the administration of bacterial endotoxin [lipopolysaccharide (LPS)], which, through the release of endogenous cytokines and other mediators, induces a physiopathological response similar to a bacterial infection. LPS was administered iv twice daily for 5 days starting on days 2-8 of the follicular phase. The stress challenge resulted in a significant lengthening of the follicular phase in all monkeys. Two distinct groups were observed. In group 1 (n = 5), the mean (+/- SE) length of the follicular phase in the LPS-treated cycle was significantly increased, from 10.2 +/- 0.2 in control cycle 2 to 30.8 +/- 4.3 days (except in one monkey that had a 4-month amenorrheic interval). In group 2 (n = 5), the length of the follicular phase significantly increased but not to exceed the duration of the LPS treatment (9.7 +/- 1.1 vs. 13.6 +/- 1.2). Estradiol concentrations decreased significantly after LPS in group 1 (34.8 +/- 5.5 vs. 16.2 +/- 6.5 pg/mL) and remained suppressed after the challenge. In group 2, estradiol levels remained stationary throughout the 5-day LPS treatment (26.0 +/- 6.5 vs. 25.6 +/- 3.9). Compared with control values at a similar stage of the follicular phase, most LH and FSH values during LPS treatment were higher than controls. Estradiol and gonadotropin surges were delayed by LPS treatment for a varying length of time according to each grp. Significant differences in integrated luteal progesterone concentrations characterized control cycles of groups 1 and 2 (group 1: 36.5 +/- 1.5, group 2: 47.5 +/- 2.6). In group 1, there were no further effects of LPS on luteal progesterone during the treatment and two post-LPS cycles. In contrast, in group 2, integrated luteal progesterone concentrations were significantly decreased in post-LPS cycle 1 (to 36.0 +/- 4.4). Cortisol significantly increased at hour 3 after each morning LPS injection but the amplitude of the response decreased over the 5-day period. Progesterone increased significantly by hour 3 after the first LPS injection but remained unchanged after subsequent LPS administration. Our data demonstrate that a 5-day inflammatory-like episode during the follicular phase can delay folliculogenesis and that damage to this process is intensified in individuals who already demonstrate a subtle cyclic degradation, in the form of decreased progesterone secretion in the luteal phases preceding the stress episode. Long-term endocrine effects, in the form of decreased luteal secretory activity in the first poststress cycle, are observed in normally cycling individuals, suggesting that inadequacy of the luteal phase may represent the first stage in the damage that a stress episode can inflict upon the normal menstrual cycle.
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PMID:Stress and the menstrual cycle: relevance of cycle quality in the short- and long-term response to a 5-day endotoxin challenge during the follicular phase in the rhesus monkey. 966 28

Interleukin (IL)-6, a multifunctional cytokine originally described as a T cell-derived factor, is also produced by different cell types, and it influences a wide variety of physiological and pathophysiological processes. Recent studies further suggest that IL-6 has a role in down-regulating hormone production by endocrine organs and can negatively affect the steroidogenic capacity of both ovaries and testes. Thus, the aims of this investigation were to examine whether IL-6 plays a role in luteolysis and, more specifically, to determine whether luteal cells express the IL-6 gene, whether this expression is developmentally and hormonally regulated in pregnancy, and whether the corpus luteum could be a target for IL-6 action. Using semiquantitative RT-PCR, messenger RNA (mRNA) encoding both components of the IL-6 receptor [the ligand-binding subunit (IL-6 R) and the IL-6 R-associated signal transducer (gp130)] were found to be highly expressed in corpora lutea throughout pregnancy. In contrast, IL-6 mRNA expression was barely detectable from day 4 through the end of pregnancy, whereas a sharp and abrupt expression of IL-6 mRNA occurred immediately after parturition. Although the corpus luteum does not express IL-6 mRNA during most of pregnancy, it could be induced to express this gene with an in vivo injection of the bacterial endotoxin, lipopolysaccharide. In addition, when corpora lutea from day-15 pregnant rats were isolated and maintained in culture, IL-6 mRNA that was undetectable at 0 h increased in a time-related manner and reached significant levels after 4 h of incubation, followed by a similar increase in IL-6 protein secreted in the culture media. Isolation of the small and large luteal cells by elutriation indicated that both cell populations can secrete IL-6 in culture. The apparent ability of luteal cells to spontaneously express IL-6 in vitro, together with the lack of IL-6 expression during most of pregnancy, led us to examine whether the IL-6 gene is silenced throughout pregnancy by luteotropic hormones. Corpora lutea from day-15 pregnant rats were cultured in the presence of different doses of progesterone; the synthetic glucocorticoid, dexamethasone; 17beta-estradiol; and PRL. Progesterone and dexamethasone markedly inhibited IL-6 mRNA expression, whereas 17beta-estradiol had a minimal inhibitory effect, and PRL did not affect IL-6 mRNA expression. In summary, results of this investigation have revealed that the rat corpus luteum expresses the IL-6 receptor system and that luteal cells are able to secrete IL-6. However, IL-6 gene expression is silenced during most of pregnancy, probably by the high levels of progesterone locally produced in the corpus luteum. The salient finding that progesterone and glucocorticoid strongly inhibit the expression of IL-6 in the corpus luteum suggests that one important luteotropic role of progesterone and glucocorticoids could be to prevent the expression of IL-6, which might have a deleterious effect on luteal function.
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PMID:The expression of interleukin-6 in the pregnant rat corpus luteum and its regulation by progesterone and glucocorticoid. 968 13

Bacterial products are thought to induce labor by stimulating the production of pro-inflammatory cytokines and prostaglandins in gestational tissues, leading to the onset of preterm parturition. Progesterone withdrawal is a prerequisite of parturition in many species. Yet a role for progesterone in the mechanisms responsible for preterm parturition, in the setting of infection, is unclear. The current studies were conducted to determine if a fall in serum progesterone concentrations occurs before the onset of bacterial product-induced preterm parturition in animals. Accordingly, pregnant mice at day 15 (70% gestation) were injected i.p. with Escherichia coli lipopolysaccharide (LPS; 50 microg/mouse) and timed-pregnant rabbits were inoculated transcervically with a suspension of E. coli to cause an ascending intrauterine infection. Control animals in both groups received equal volumes of sterile phosphate-buffered saline (PBS) solution. Blood specimens were collected at regular intervals and serum progesterone levels were determined by RIA. Within 14 h of LPS administration, mice delivered their pups. The median concentrations of serum progesterone were significantly lower at 1 h, 4 h, 10 h, and at the onset of preterm parturition (11-12 h) after LPS injection, compared to that in animals given PBS. Similarly, E. coli-inoculated rabbits delivered 1-2 days posttranscervical inoculation and demonstrated 60% decrease in serum progesterone within 12-24 h of inoculation compared to those given PBS. Parturition in both control groups occurred at term, following typical progesterone withdrawal. It is concluded that LPS administration to pregnant mice and ascending intrauterine infection in pregnant rabbits is associated with a dramatic fall in serum progesterone concentrations prior to the onset of parturition.
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PMID:Bacteria-induced or bacterial product-induced preterm parturition in mice and rabbits is preceded by a significant fall in serum progesterone concentrations. 977 89

Nitric oxide (NO) is synthesized by NO synthases (NOS) from L-arginine in a variety of tissues, including rat uterus. Progesterone was shown to be required for maintaining elevated NOS II expression in pregnant rat uterus. However, effects of estrogens on uterine NOS II expression remains unclear. In the present study, we examined whether 17beta-estradiol regulates NO production and NOS II expression in the rat uterus during pregnancy and in nonpregnant rats treated with lipopolysaccharide (LPS). Rats on Day 18 of pregnancy received 17beta-estradiol (0.5 or 5 microgram/rat). Groups of ovariectomized (ovx) rats received 17beta-estradiol (5 microgram/rat) or LPS (1 mg/rat) or a combination of the two or received vehicle only. All rats were sacrificed 24 h after treatments. Nitrite concentrations in uterine cultures were measured by Greiss reaction. Uterine NOS II and NOS III proteins and mRNA levels were determined by Western blotting and reverse transcription polymerase chain reaction, respectively. In the pregnant rat, estradiol administration caused inhibition in total NO production, suppression of both mRNA and protein levels of NOS II enzyme, and increase in NOS III mRNA and protein levels in the uterus in a dose-dependent manner. The data indicate that estradiol inhibits NOS II and total NO generation and stimulates NOS III expression. In ovx rats, LPS stimulated NOS II mRNA and NO production by the uterus. Coadministration of 5 microgram estradiol profoundly suppressed NOS II mRNA and NO generation but elevated NOS III mRNA. Thus, estradiol inhibited LPS-induced increases in NOS II mRNA. Estradiol inhibits NO production by NOS II through the inhibition of NOS II expression in the rat uterus. This inhibition of NOS II expression occurs whether NOS II expression is constitutive (pregnancy) or induced (LPS-treated nonpregnant). Estradiol inhibition of NOS II expression occurs in the presence (pregnancy) or absence (ovx) of progesterone. Estradiol may play a role in regulating NOS II expression and NO production and uterine contractility during pregnancy and labor.
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PMID:Estradiol-17beta inhibits nitric oxide synthase (NOS)-II and stimulates NOS-III gene expression in the rat uterus. 1085 39


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