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)

To determine the degree of similarity between pituitary and lymphocyte proopiomelanocortin, the lymphocyte mRNA was reverse transcribed, cloned, and sequenced. Murine lymphocyte mRNA was first purified by oligo(dT)-cellulose affinity chromatography and was reverse transcribed by using a selective 3' antisense oligonucleotide primer directed at the boundary between the translated/nontranslated region on the 3' end of exon 3. This cDNA was then amplified in a polymerase chain reaction with selective primers containing Sal I and Kpn I restriction endonuclease sites. Amplified cDNA was then directionally ligated into M13mp18 and M13mp19 bacteriophage and was sequenced. The nucleotide sequence encoding this peptide was identical to that of mouse pituitary corticotropin (ACTH). Elevated levels of lymphocyte immunoreactive ACTH were then induced with bacterial lipopolysaccharide and the peptide(s) was purified by antibody affinity chromatography and reverse-phase high-performance liquid chromatography. The predominant immunoreactive ACTH species was approximately 3 kDa and its sequence was identical to pituitary ACTH(1-25). These results conclusively demonstrate that lymphocytes produce authentic ACTH and harbor its mRNA.
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PMID:Nucleotide and amino acid sequence of lymphocyte-derived corticotropin: endotoxin induction of a truncated peptide. 168 57

Peripheral mononuclear (PMN) cells are known to produce ACTH-like immunoreactivity (ACTH-LIR) in vitro. Based on these findings the aim of this study was to find out whether thymopentin (the active pentapeptide of the native hormone thymopoietin) may stimulate ACTH-LIR production and release by cultured normal human lymphocytes. Thymopentin at concentration of 1 microgram/ml was capable of inducing ACTH-LIR release by normal human PMN cells (median 22 pg/ml) whereas ACTH-LIR inside cells was lower (median 11 pg/10(7) cells). The chromatographic characterization of the eluted material identified the presence of ACTH immunoreactive peptides with the elution characteristics of the precursors 31 K proopiomelanocortin, 22 K ACTH and 4.5 K ACTH, together with higher molecular weight material (greater than 43 K). These data demonstrate that thymopentin induces ACTH-LIR release by human lymphocytes, thus adding a novel factor to those already reported (corticotrophin releasing factor, lipopolysaccharide, viruses) capable of such function.
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PMID:Thymopentin induces release of ACTH-like immunoreactivity by human lymphocytes. 256 68

We have discovered that the immune system processes proopiomelanocortin (POMC) products differently depending on the stimulus for induction. We have shown that corticotropin-releasing factor (CRF) induces the lymphocytes from C3HeB/FeJ lipopolysaccharide (LPS)-sensitive mice to produce adrenocorticotropin (ACTH) 1-39 and beta-endorphin, whereas LPS induces these lymphocytes to produce ACTH 1-23 to 26 and alpha- or gamma-endorphin. We have proposed that the smaller species of ACTH and endorphin are proteolytic cleavage products from ACTH 1-39 and beta-endorphin. Analysis of C3HeB/FeJ LPS-treatment B lymphocyte lysates showed an enzymatic activity at pH 5 but not pH 7 that cleaved ACTH 1-39 into a smaller ACTH 1-23 to 26. The B lymphocytes from C3H/HeJ (LPS-resistant) mice expressed but did not process proopiomelanocortin after LPS or CRF treatment, nor did their B cells express the aforementioned enzymatic activity. Taken together, these data suggest a unique processing pathway in LPS-treated B lymphocytes and one in which immunoreactive (ir)-endorphins may play a role in the pathophysiology of endotoxic shock.
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PMID:Novel processing pathway for proopiomelanocortin in lymphocytes: endotoxin induction of a new prohormone-cleaving enzyme. 282 3

alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of alpha-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and alpha-MSH production in RAW 264.7 cultured murine macrophages stimulated with bacterial lipopolysaccharide and interferon gamma. alpha-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. alpha-MSH increased cAMP accumulation in RAW cells, characteristic of alpha-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary alpha-MSH receptor (melanocortin 1). mRNA for proopiomelanocortin, the precursor molecular of alpha-MSH, was expressed in RAW cells, and tumor necrosis factor alpha increased production and release of alpha-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor alpha can induce macrophages to increase production of alpha-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of NO. The results suggest that alpha-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.
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PMID:Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone. 754 12

Antipyretic properties have been ascribed to arginine vasopressin (AVP), and the site where its antipyretic effects are mediated in the brain was identified as the ventrolateral septum of the limbic system. In guinea pigs, the majority of AVP projections to the septum originate from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). Electrical stimulation of the PVN with 10-s trains of current pulses (duration 1 ms, frequency 20 Hz, amplitude 8 V, current 0.205 +/- 0.017 mA) reduced the febrile response to an intramuscular injection of 20 micrograms/kg lipopolysaccharide (LPS from Escherichia coli, 0111: B4) by 54% compared with unstimulated animals. This reduction in fever by electrical PVN stimulation was partly reversed by a simultaneous intraseptal microinfusion of the vasopressinergic V1-receptor antagonist d(CH2)5[Tyr(Met)2]AVP at a concentration of 10(-5) mol for 6 h with an infusion speed of 0.1 microliter/min. We further investigated the effects of intraseptal microinfusions or systemic infusions of the gamma-melanocyte-stimulating hormone (gamma-MSH), a derivative of the proopiomelanocortin, on LPS-induced fever. Intraseptal microinfusions of gamma-MSH at a concentration of 10(-5) mol/l for 6 h with an infusion speed of 0.1 microliter/min caused a 38% reduction in fever. A significantly greater 57% reduction in fever was observed when the intraseptal microinfusion of gamma-MSH was combined with electrical stimulation of the PVN (for parameters see above). A systemic infusion of 0.261 mumol gamma-MSH for 6 h reduced LPS fever to approximately 50% compared with animals infused with vehicle (0.9% saline).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antipyresis caused by stimulation of vasopressinergic neurons and intraseptal or systemic infusions of gamma-MSH. 814 22

We have investigated the role of circulating glucocorticoids in the suppression of the hypothalamic-pituitary-thyroid (HPT) axis following lipopolysaccharide (LPS) injection in rats. Intraperitoneal injection of LPS (2.5 mg/kg) suppressed paraventricular nucleus thyrotropin-releasing hormone (TRH) mRNA, pituitary thyroid-stimulating hormone (TSH) mRNA and plasma triiodothyronine. In these animals LPS also increased paraventricular nucleus corticotropin-releasing hormone (CRH) mRNA, pituitary proopiomelanocortin (POMC) mRNA and plasma corticosterone levels. To investigate the role of plasma corticosterone in the suppression of the HPT axis, we clamped the plasma corticosterone level at morning baseline level by bilateral adrenalectomy and corticosterone pellet implantation. Ten days after surgery, LPS injection evoked a dramatic increase in CRH mRNA and POMC mRNA. Despite the lack of change in plasma corticosterone in the corticosterone-clamped rats, LPS was still able to suppress TRH and TSH mRNA levels in both corticosterone-clamped and sham-operated rats. These data indicate that in response to LPS, suppression of the HPT axis occurs and is independent of the LPS-induced increase in plasma corticosterone.
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PMID:Inhibition of the hypothalamic-pituitary-thyroid axis in response to lipopolysaccharide is independent of changes in circulating corticosteroids. 952 63

Neuropeptide and cyclooxygenase (Cox) gene expression was examined in the brains of catheterized pigs killed 30 or 120 min after intravenous injection of a low (20 microg) dose of lipopolysaccharide endotoxin (LPS), previously demonstrated to induce fever in this species. In the paraventricular hypothalamic nucleus (PVN), corticotrophin releasing hormone (CRH) mRNA was shown to be present in the pars parvocellularis but was not upregulated 30 or 120 min after 20 microg LPS, or 90 min after 60 microg LPS; there was also no change in proopiomelanocortin (POMC) message in the anterior pituitary (AP). Similarly, expression of mRNAs for lysine vasopressin (LVP) or oxytocin (OT) did not change in the PVN after LPS (20 microg), although LVP message was increased (p<0.05) at 30 min in the hypothalamic supraoptic nucleus (SON). Expression of Cox-1 and Cox-2 genes was quantified in the organum vasculosum lamina terminalis (OVLT) and choroid plexus (CP) in an attempt to determine whether altered expression of prostaglandin (PG) synthetic enzymes in brain vasculature is involved in LPS fever. Although vascular endothelial cells in both structures expressed Cox-1 and Cox-2 mRNAs, neither increased in the OVLT following LPS. However, in the CP, Cox-1 mRNA was enhanced (p<0.05) at 30 and 120 min after LPS injection and Cox-2 showed a similar (NS) change. These results provide the first description of CRH and Cox gene expression in the porcine brain. They also suggest that LPS may influence the activity of genes controlling LVP synthesis in the hypothalamus and PG production by the brain vasculature.
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PMID:Expression of mRNAs for vasopressin, oxytocin and corticotrophin releasing hormone in the hypothalamus, and of cyclooxygenases-1 and -2 in the cerebral vasculature, of endotoxin-challenged pigs. 984 5

This study determined the effects of feeding status on basal and lipopolysaccharide (LPS)-stimulated cytokine and neuropeptide gene expression in the hypothalamus. With the use of RNase protection assays, we measured mRNA levels of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1RA), IL-1 receptor type I (IL-1RI), IL-1R accessory proteins (AcP I and II), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), glycoprotein 130 (Gp 130), leptin receptor (OB-R), neuropeptide Y (NPY), preprodynorphin, and proopiomelanocortin (POMC). Analyses were done in ad libitum-fed, fasted, and fasted and refed rats treated with the intracerebroventricular administration of physiological saline or LPS. The data show that food deprivation increases the basal mRNA expression of IL-1beta, IL-1RA, TNF-alpha, IL-1RI, and IL-1R AcP I, whereas mRNA levels of POMC showed a decrease. Five hours of refeeding returned cytokine levels to those observed in the ad libitum-fed group. LPS administration induced a robust upregulation of IL-1beta, TNF-alpha, and IL-1RI during all three feeding conditions. Acute food deprivation did not modulate LPS-induced changes in hypothalamic cytokine mRNA profiles. These findings show that 1) cytokine modulation occurs as an adaptive response to the stress of acute fasting and 2) acute fasting does not affect LPS-induced cytokine mRNA modulation in the hypothalamus. The data have implications to gram-negative infections associated with acute anorexia.
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PMID:Feeding status and bacterial LPS-induced cytokine and neuropeptide gene expression in hypothalamus. 1051 61

Anorexia and weight loss are manifestations of inflammation seen both in patients and in experimental animal models such as the lipopolysaccharide (LPS)-treated rat. Using in situ hybridization, the levels of mRNAs encoding proopiomelanocortin (POMC), neuropeptide Y (NPY), galanin, melanin-concentrating hormone (MCH) and cocaine- and amphetamine-regulated transcript (CART) were investigated in the rat hypothalamus after a single intraperitoneal dose (125 microg/kg) of LPS. Four hours after LPS injection the food intake was significantly decreased. POMC and CART mRNA levels were increased in the arcuate nucleus, and MCH, CART and galanin mRNAs were all decreased in the lateral hypothalamic area in LPS-treated rats. Levels of mRNAs for NPY and galanin in the arcuate nucleus, and for MCH and CART in the zona incerta did not change significantly after LPS treatment. These findings support the hypothesis that LPS-induced factors mediate signalling to the POMC/CART neurons in the arcuate nucleus which could lead to reduced food intake by decreasing MCH, CART and galanin synthesis in target lateral hypothalamic neurons.
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PMID:Effect of LPS administration on the expression of POMC, NPY, galanin, CART and MCH mRNAs in the rat hypothalamus. 1140 87

A study was conducted with 20 weaned barrows (14 d, 4.98 +/- 0.21 kg) to determine the effect of feeding spray-dried plasma (SDP) after weaning on the pig's stress response to a lipopolysaccharide (LPS) challenge. After weaning, pigs were fed a diet containing 0 or 7% SDP for 7 d. On d 6 after weaning, all pigs were nonsurgically fitted with a jugular catheter. On d 7 after weaning, the pigs were given i.p. injections of either saline or LPS (150 microg/kg BW) followed by serial blood collection every 15 min for a 3-h period. Following the 3-h blood collection, all pigs were killed and tissue was collected for mRNA analysis. Pig weight on d 7 after weaning was not affected by dietary treatment (P > 0.21). Pigs fed the diet with SDP had lower (P < 0.05) levels of hypothalamic corticotropin-releasing hormone (CRH) mRNA, pituitary gland CRH receptor mRNA, and adrenal gland adrenocorticotropin-releasing hormone (ACTH) receptor mRNA. Dietary treatment did not affect pituitary gland proopiomelanocortin (POMC) mRNA. No effect of LPS treatment was observed in any of the mRNA levels examined. For both serum ACTH and cortisol, there was a significant diet x LPS treatment interaction (P < 0.01) such that both the ACTH and cortisol responses to the LPS challenge were greater in the pigs fed the diet with SDP than in the pigs fed the diet without SDP. For pigs given the saline injection, diet did not affect basal serum cortisol concentration; however, basal serum ACTH concentration was lower in those pigs fed the diet with SDP (P < 0.0001). A diet x LPS treatment interaction (P < 0.024) was observed for adrenal gland mRNA expression for steroidogenic acute regulatory (StAR) protein such that the LPS-induced increase in StAR mRNA was greater in the pigs fed SDP than in pigs fed the diet without SDP. These results demonstrate that pigs fed a diet with SDP have an increased activation of the pituitary-adrenal axis following an LPS challenge compared to pigs fed a diet without SDP.
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PMID:Effect of spray-dried plasma and lipopolysaccharide exposure on weaned pigs: II. Effects on the hypothalamic-pituitary-adrenal axis of weaned pigs. 1188 34


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