UNIPROT:P43026 - FACTA Search

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)

The immune system and the hypothalamic-pituitary-adrenal (HPA) axis play important role in the overall inflammatory response. The mechanism through which lipopolysaccharide (LPS, endotoxin) stimulates the HPA axis is not well understood. In order to clarify the role of hypophysiotropic peptides of paraventricular origin in the effect of LPS on ACTH and corticosterone secretion, the effect of LPS was studied on rats with lesions of hypothalamic paraventricular nucleus (PVN). It was shown that 90 min after 2 mg/kg LPS i.p. the ACTH, but not the corticosterone response was effectively blunted in PVN-lesioned rats, as compared to sham operated animals. However, in PVN-lesioned rats 240 min after treatment with LPS a significantly higher plasma ACTH and corticosterone level was monitored. It is, therefore, suggested that in response to LPS activation of HPA both CRF(s)-dependent and CRF(s)-independent mechanisms are involved, even a direct effect of the adrenal cortex should be taken into account.
...
PMID:CRF-dependent and CRF-independent mechanisms involved in hypophysial-adrenal system activation by bacterial endotoxin. 134 88

Bacterial lipopolysaccharide (LPS) and corticotropin releasing hormone (CRH) plus arginine vasopressin (AVP) induce immunoassayable (1-13)ACTH (alpha MSH) from mononuclear leukocytes. We studied the ability of LPS and CRH + AVP to in vitro stimulate native ACTH (not alpha MSH) and substance P (SP) production and thymidine incorporation in human mononuclear leukocytes. Neither CRH + AVP nor LPS stimulated detectable amounts of intracellular or extracellular ACTH (less than 15 pg/8 x 10(6) cells or total medium) or SP (less than 50 pg/8 x 10(6) cells or total medium) at 1, 2, 3 or 4 days of incubation. LPS, but not CRF + AVP, increased the amount of 3H-thymidine incorporation over controls. This data questions the importance of an immunoadrenal axis and the synthesis of SP by mononuclear leukocytes.
...
PMID:Corticotropin releasing hormone and arginine vasopressin stimulation of ACTH and substance P in human mononuclear leukocytes. 169 18

Modification of the cellular immune response in uraemia is partly responsible for the increased susceptibility to infection found in dialysis patients. In order to study this further we have evaluated the in vitro production of tumour necrosis factor (TNF) by peripheral-blood monocytes (PBMCs) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure. The patients were subdivided into two groups according to the type of dialysis: those undergoing haemodialysis (HD; n = 12) and continuous ambulatory peritoneal dialysis (CAPD; n = 18). Results were compared with those of controls taken from healthy laboratory staff (n = 7). The experiments show that the secretion of TNF by of TNF by PBMCs in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 vs. 18.2 +/- 13.3 U/ml, mean +/- SD, p less than 0.001) and controls (81.3 +/- 38.7 vs. 18.1 +/- 6.6 U/ml, p less than 0.001). There was no significant difference between the CAPD group and controls. In vitro production of TNF fell slightly following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, p less than 0.05). We conclude from this study that TNF release from PBMCs is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD, in vitro. TNF release, however, is suppressed immediately following a single HD session. We suggest that HD rather than uraemia per se up-regulates monocyte secretion of TNF in vitro and that this is not an immediate response to activation by membrane polymer.
...
PMID:Evaluation of the in vitro production of tumour necrosis factor by monocytes in dialysis patients. 180 56

The cytokine interleukin-1 (IL-1) has a variety of effects in the kidney involving induction of nephritis and renal injury. In addition, recent reports suggest that IL-1 regulates natriuresis and renin secretion in the kidney. To examine the potential sites of action of IL-1 in the kidney, we used iodine-125-labeled recombinant human interleukin-1 alpha ([125I]IL-1 alpha) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) kidney. The binding of [125I] IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant (Kd) of 66 +/- 10 pM and a maximum number of binding sites of 1.04 +/- 0.24 fmol/mg protein. In competition studies, recombinant human IL-1 alpha, recombinant human IL-1 beta, and a weak IL-1 beta analog (IL-1 beta+) inhibited [125I]IL-1 alpha binding to mouse kidney in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constant (Ki) values of 28 +/- 19, 53 +/- 23, and 5560 +/- 2098 pM, respectively; rat/human CRF and human tumor necrosis factor had no effect on [125I]IL-1 alpha binding. In autoradiographic studies, IL-1 receptors were heterogeneously distributed in the kidney, with significantly higher densities present in the medulla than in the cortex. To study the effects of endogenous IL-1 in modulating [125I]IL-1 alpha-binding sites in kidney, we injected 30 micrograms of the bacterial endotoxin lipopolysaccharide (LPS) to mice ip. Autoradiographic studies demonstrated substantial decreases in [125I]IL-1 alpha binding in both the kidney cortex (control, 34.7 +/- 6.2 fmol/mg tissue equivalent; LPS, 11.3 +/- 0.3; P less than 0.05) and medulla (52.7 +/- 8.1 vs. 26.0 +/- 1.0; P less than 0.05) 24 h after injection of LPS. Saturation studies in whole kidney homogenates demonstrated that the LPS-induced decrease in [125I]IL-1 alpha binding was primarily due to a down-regulation of IL-1 receptors (i.e. decrease in the maximum number of binding sites). The identification of IL-1 receptors in kidney with characteristics similar to those of IL-1 receptors in the brain-endocrine-immune axis provides further support for a physiological role for IL-1 in regulating renal function.
...
PMID:Interleukin-1 receptors in mouse kidney: identification, localization, and modulation by lipopolysaccharide treatment. 182 79

We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25-hydryoxyvitamin D (25OHD) to anephric humans. Since normal alveolar macrophages are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or lipopolysaccharide, we determined whether macrophages derived from peripheral blood monocytes could be an extrarenal source of 1,25-(OH)2D3. Our results demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3. The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4 +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA. The activity of this enzyme was reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3 in the incubation medium. Normal macrophages further hydroxylated 1,25-(OH)2D3 to more polar metabolites, and this catabolic activity was significantly enhanced by physiological concentrations of 1,25-(OH)2D3. In chronic renal failure, peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/- 0.8 vs. 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a decreased capacity to degrade 1,25-(OH)2D3. Exogenous 1,25-(OH)2D3, in physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/- 8.5%) comparable to that observed in normal cells. 1,25-(OH)2D3 production by macrophages did not correlate with the severity of hyperparathyroidism. Moreover, human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L) did not stimulate the 1 alpha-hydroxylase activity of macrophages from either normal or uremic subjects. These results demonstrate that 1) normal peripheral macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in chronic renal failure.
...
PMID:Extrarenal production of calcitriol in normal and uremic humans. 198 15

The purpose of our study was to set up a reliable method for the measurement of complement activation by adapting the method of crossed immunoelectrophoresis. We utilised anti C3 antiserum and barbitone buffer, containing sufficient EDTA to prevent in vitro activation of complement. We studied 44 patients undergoing open heart surgery, with cardiopulmonary bypass (CPB) by the analysis of plasma samples taken during the operation, and also samples of plasma and dialysate effluent from patients with end stage renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD). Measurements were also carried out on stored blood, aged serum and serum treated with varying doses of lipopolysaccharide (LPS). Complement activation occurs in 95% of patients during CPB with levels ranging from less than 4.5% to 11.3% of total C3, but there was no detectable activation in any pre-bypass sample. Negligible complement activation occurs in the plasma of CAPD patients, but the dialysate effluent gave results from undetectable levels to 31.7%, in the absence of clinical peritonitis. Variable in vitro complement activation occurs in aged serum, but it was not detectable in stored blood. Serum treated with LPS showed levels of activation directly proportional to the dose of LPS and measurable at a level of 0.1 microgram/ml of serum. The method had a coefficient of variation of 4.5%, and provides a reliable way of measuring complement activation in clinical situations such as cardiopulmonary bypass and peritoneal dialysis.
...
PMID:Clinical applications of crossed immunoelectrophoresis to the study of complement activation. 343 39

Intracerebroventricular administration in rats of heat inactivated Mycoplasma fermentans caused a dose- and time-dependent increase in serum adrenocorticotrophin (ACTH) and corticosterone (CS). In rats with complete deafferentation of the mediobasal hypothalamus, which markedly depleted the median eminence CRF-41, the ACTH and CS responses to M. fermentans were completely inhibited. Pretreatment with dexamethasone abolished the adrenocortical response to M. fermentans. In lipopolysaccharide (LPS) unresponsive C3H/HeJ mice LPS failed to induce the adrenocortical response while administration of M. fermentans elicited a normal CS response. These results suggest that: M. fermentans can activate the hypothalamo-pituitary-adrenal axis via a central mechanism which involves hypothalamic ACTH secretagogue(s), and this effect is sensitive to the negative feedback of glucocorticoids. It is possible that the elevated glucocorticoid levels resulting from mycoplasma infection may be involved in the pathogenesis of mycoplasma-associated diseases.
...
PMID:Mycoplasma fermentans activates the hypothalamo-pituitary adrenal axis in the rat. 761 81

This study extends the neuroendocrine role of central interleukin-1 beta (IL-1 beta) during the stress of lipopolysaccharide (LPS) challenge to include inhibition of the somatotropic [GH-releasing hormone (GHRH)-somatostatin (SRIF)-GH] axis in juvenile male rats and clarifies the role of CRF in the mediation of LPS/IL-1-induced changes in GHRH and SRIF neurosecretion. The results of the in vivo component of this study demonstrated that LPS treatment (2.5 mg/kg twice daily for 5 days) caused a significant attenuation of body weight gain for 2 days (2.4 +/- 1.7% vs. 10.3 +/- 1.8% BW/day in saline controls; P < 0.05) and failure of catch-up growth thereafter even though a small transient suppression of food intake returned to normal by the second of 4 days of treatment. Associated with the first day of growth attenuation was an acute suppression of all plasma GH parameters, including GH mass (area under the curve, 1.972 +/- 0.1837 vs. 6.402 +/- 1.7 micrograms/ml.6 h for saline controls; P < 0.05), in animals receiving an acute bolus of LPS, which was blocked by prior microinjection of IL receptor antagonist protein (IRAP) into the third ventricle. In contrast, GH parameters associated with the second day of LPS-suppressed body weight gain were increased (GH mass, 9.4 +/- 2.2 vs. 3.5 +/- 0.5 micrograms/ml.4 h in saline controls; P < 0.05). These increases were reversed after another 2 days of LPS treatment. In a series of in vitro experiments using medial basal hypothalamic (MBH) explants incubated with LPS [100 ng/ml alone or with 10(-7) M IRAP or 10(-6) M CRF antagonist (CRF-ANT)], GHRH release from MBH incubated with LPS was significantly greater than that in controls (231 +/- 79% vs. 71 +/- 34% of baseline release; P < 0.05), and this stimulation was antagonized by both IRAP and CRF-ANT. SRIF release was significantly increased by incubation with LPS (163 +/- 28% vs. 97 +/- 20% of the baseline for controls; P < 0.05) and blocked (to 88 +/- 14% of the baseline) by IRAP, but not by CRF-ANT. Finally, when MBH explants were incubated with IL-1 beta (10(-9) M), there was a significant inhibition of in vitro GHRH release (37.9 +/- 6.7% vs. 74.9 +/- 16.6% for controls), which was reversed by IRAP and CRF-ANT, and a significant stimulation of SRIF release (168.7 +/- 37.5% vs. 98.0 +/- 11.6% for controls), which was reversed by IRAP, but not CRF-ANT.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Endotoxin-induced suppression of the somatotropic axis is mediated by interleukin-1 beta and corticotropin-releasing factor in the juvenile rat. 762 73

The present study investigated the effect of intraperitoneal (i.p.) administration of endotoxin lipopolysaccharide (LPS) and immobilization stress on the genetic expression of corticotropin-releasing factor receptor (CRF-R) in the brains of conscious male Sprague-Dawley rats. One group of rats was killed at 1, 3, 6, 9, and 12 hr after a single intraperitoneal injection of either the LPS (250 micrograms/100 gm of body weight) or the vehicle solution; the other group was killed before, immediately after, 1.5, 3, 6, and 12 hr after a 90 min acute session of immobilization stress. Rats were deeply anesthetized and rapidly perfused with a solution of 4% paraformaldehyde-borax. Frozen brains were mounted on a microtome and cut from the olfactory bulb to the medulla in 30 microns coronal sections. mRNA encoding the rat CRF-R was assayed by in situ hybridization histochemistry using a 35S-labeled riboprobe, and CRF-R localization within CRF-immunoreactive neurons in the PVN was determined using a combination of immunocytochemistry and in situ hybridization techniques. Strong basal levels of CRF-R transcripts were observed in several regions of the brain (piriform cortex, medial and basolateral nuclei of the amygdala, red nucleus, pontine gray, cerebellum, laterodorsal tegmental nucleus, caudal division of the zona incerta, nucleus incertus, spinal and principal sensory nuclei of the trigeminal nerve, and various layers of the cortex). A low to moderate signal was also detected in multiple sites (medial septal nucleus, nucleus of the diagonal band, supraoptic nucleus, arcuate nucleus of the hypothalamus, interpeduncular nucleus, and nucleus prepositus). Whereas vehicle-treated and control rats displayed hardly detectable signals of CRF-R mRNA in the paraventricular nucleus (PVN), CRF-R gene transcription was highly stimulated by LPS administration and immobilization stress in this hypothalamic structure. Indeed, the CRF-R mRNA signal was positive in the dorsomedial parvocellular PVN 3 hr after LPS injection, strong and maximum in both parvo- and magno-PVN at 6 hr postinjection, and declined 9 and 12 hr after treatment. Similarly, 90 min and 3 hr after the immobilization session, mRNA encoding the CRF-R was highly expressed in the parvo-PVN and totally vanished 12 hr after the stress. A lower but significant increase in the CRF-R transcript signal was also observed in the supraoptic nucleus 6 hr after the LPS treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Immune challenge and immobilization stress induce transcription of the gene encoding the CRF receptor in selective nuclei of the rat hypothalamus. 772 22

Cellular release of cytokines may be responsible for certain complications of extracorporeal dialysis including the increased susceptibility to infection found in dialysis patients. In order to study this further, we have evaluated the in vitro production of tumor necrosis factor (TNF) by peripheral blood monocytes (PBMC) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure (ESRF). The patients were subdivided into two groups according to the type of dialysis; those undergoing hemodialysis (HD) (N = 12) and those performing continuous ambulatory peritoneal dialysis (CAPD) (N = 9). Results were compared with those of controls taken from healthy laboratory staff (N = 7). The experiments show that the secretion of TNF by PBMC's in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 U/ml vs. 18.2 + 13.3 U/ml, mean +/- SD, P < 0.001); and controls (81.3 +/- 38.7 U/ml vs. 18.1 +/- 6.6 U/ml, P < 0.001). There was no significant difference between the CAPD group and controls. In vitro monocyte production of TNF fell following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, P < 0.05). We conclude from this study that TNF release from PBMC's in vitro is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD. Interestingly, TNF release from monocytes collected immediately following a dialysis was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:In vitro production of tumor necrosis factor by monocytes cultured from dialysis patients. 832 Sep 27

1 2 3 4 5 6 Next >>