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 presence of a Tumor Necrosis Factor alpha (TNFalpha)-like molecule has been suggested in fish by biological assays and biological and antigenic cross-reactivities with human TNFalpha. In the present study, whether rainbow trout macrophages produce TNFalpha was examined. Murine recombinant TNFalpha (m-rTNFalpha) was used as the standard mammalian TNFalpha. The supernatants were harvested from trout macrophage culture stimulated with lipopolysaccharide (LPS) and then passed through a Polymyxin B column to remove LPS. Results show that trout macrophage culture supernatants exhibit TNF-like activities. The supernatants significantly enhanced neutrophil migration and macrophage respiratory burst activity as assessed by NBT reduction test. The supernatants were also highly cytotoxic to murine L929 cells, which are known to be sensitive to mammalian TNFalpha. The biological activities of TNF in the trout macrophage culture supernatant was determined as 2.6 U ml(-1) in the presence of actinomycin D. This indicates biological cross-reactivity of trout TNFalpha-like factor on mammalian cells. Moreover, these activities were inhibited by a rabbit anti-mTNFalpha antibody. These results suggest that rainbow trout macrophages produce a TNFalpha-like factor that is similar to the mammalian TNFalpha in functions.
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PMID:Tumor necrosis factor alpha (TNFalpha)-like factor produced by macrophages in rainbow trout, Oncorhynchus mykiss. 1139 91

The purpose of the study was to investigate the course of the zymosan-induced multiple organ dysfunction syndrome (MODS) in the absence of tumor necrosis factor (TNF) in a murine model. Tumor Necrosis Factor-alpha-lymphotoxin-a knockout (TNF/LT-/-) mice (n = 36) and wild-type (TNF/LT+/+) mice (n = 36) received 40 microg of lipopolysaccharide (LPS) intraperitoneally followed by zymosan at a dose of 1 mg/g body weight 6 days later (day 0). Animals were monitored daily for body weight and temperature and clinical symptoms. At day 22, most of the surviving mice were killed to examine organ weight and histology. A small number of animals were followed until day 48. In all animals, zymosan induced an acute sterile peritonitis phase followed by an apparent recovery. From day 8 onwards the TNF/LT+/+ mice entered a third-MODS-like-phase, characterized by loss of body weight, decreased body temperature, and significant mortality. At day 22, survival in the TNF/LT-/- mice (92%) was significantly (P = 0.01) higher than in the TNF/LT+/+ mice (60%). In addition, average body temperature and average relative (vs. weight at day 0) body weight were higher in the TNF/LT-/- mice than in the TNF/LT+/+ mice (35.9 degrees C and 100% vs. 33.3 degrees C and 84%, respectively). However, at this time point, surviving animals from both groups showed similar and significant organ damage, indicated by an increase in absolute and relative (vs body weight) weight of lung, spleen, and liver (liver only in the TNF/LT-/- mice). Moreover, histopathological examination of organs from the surviving animals showed a similar degree of microscopic damage in both groups. Interestingly, besides mononuclear cells, inflammatory infiltrates in lungs and livers of TNF/LT+/+ but not of TNF-/- mice contained neutrophils. In conclusion, TNF-deficient mice exhibit significantly improved morbidity and mortality during zymosan-induced MODS. However, the absence of TNF does not completely protect against MODS in this murine model.
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PMID:Improved survival of TNF-deficient mice during the zymosan-induced multiple organ dysfunction syndrome. 1206 82

We used beta-endorphin-deficient mice as a novel approach to confirm the physiological role that opioid peptides play in the development or regulation of the immune system. We found that mice lacking beta-endorphin possessed an enhanced immune response, measured in terms of splenocyte proliferation and interleukin (IL)-2 mRNA levels, in vitro production of the splenic macrophage inflammatory cytokines IL-6 and Tumor Necrosis Factor (TNF)-alpha and plasma IL-6 following lipopolysaccharide (LPS) administration. beta-Endorphin-deficient mice had attenuated increases of plasma ACTH and corticosterone levels in response to LPS. These results are consistent with a postulated inhibitory role of endogenous beta-endorphin on the immune system at multiple levels.
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PMID:Increased splenocyte proliferative response and cytokine production in beta-endorphin-deficient mice. 1245 44

The cause of Parkinson's disease (PD) is currently unknown. Although a genetic cause has been implicated in familial PD, the vast majority of cases are considered idiopathic. Environmental toxins have been implicated as a cause for PD by many investigators. Unfortunately, the magnitude of this exposure would likely need to be very high and as a result, would likely have been identified by the many epidemiological studies performed to date. Recently, we inadvertently realized that exposure to neurotoxins while still in utero may also represent a risk factor. Thus, exposure to the bacteriotoxin, lipopolysaccharide (LPS) during a critical developmental window in rats, leads to the birth of animals with fewer than normal dopamine (DA) neurons. This DA neuron loss is apparently permanent as it is still present in 16 months old animals (the longest period studied to date). Moreover, the loss of DA neurons seen in these animals increases with age thereby mimicking the progressive pattern of cell loss seen in human PD. The DA neuron loss is accompanied by reductions in striatal DA, increases in DA activity, and increased production of the pro-inflammatory cytokine Tumor Necrosis Factor alpha (TNF-alpha). These are also characteristics of the PD brain. This model therefore shares many of the same characteristics with PD, and most importantly exhibits a slow, protracted loss of DA neurons - a characteristics of this animal model not found in other models. Interestingly, a common complication of pregnancy is a condition known as bacterial vaginosis (BV), which is known to produce increased levels of LPS and pro-inflammatory cytokines in the chorioamniotic environment of the fetus. This raises the interesting possibility that BV may be a risk factor for PD. The possibility that prenatal toxin exposure may contribute to the development of a neurodegenerative disease of the aged raises interesting new pathogenic questions and draws attention to the possibility that in utero exposure to neurotoxins may represent a here to fore unrecognized cause of PD.
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PMID:Prenatal exposure to the bacteriotoxin lipopolysaccharide leads to long-term losses of dopamine neurons in offspring: a potential, new model of Parkinson's disease. 1295 70

To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.
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PMID:Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice. 1628 65

Corticotropin-releasing factor (CRF), the principal regulator of the hypothalamus-pituitary-adrenal (HPA) axis, also modulates the inflammatory response directly, via its effect on mast cells and macrophages. On macrophages, it augments production of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines. CRF and its related peptides may also act as anti-inflammatory agents. Aim of the present work was to examine the role of macrophages on the anti-inflammatory effects of CRF-peptides and the mechanism involved. Thus, we examined if CRF receptor 1 (CRF1) and CRF2 agonists exert any anti-inflammatory effect on primary mouse macrophages. We have found that: (a) CRF, Urocortin (UCN)1 and UCN2 transiently suppressed the release of Tumor Necrosis Factor-alpha (TNF-alpha) in LPS-activated macrophages, an effect peaking at 4 h. This effect did not involve changes on TNF-alpha transcription. (b) CRF peptide-induced suppression of TNF-alpha release depended on induction of COX-2 and PGE2 synthesis. (c) Use of specific CRF1 and CRF2 antagonists suggested that this effect involved both CRF receptor types. (d) The effect of CRF-peptides on COX-2 was mediated via PI3K and p38MAPK. (e) Longer exposure of macrophages to CRF-peptides resulted in induction of TNF-alpha production via enhancement of its transcription. In conclusion, this is the first report suggesting that CRF1 and CRF2 agonists exert a biphasic effect on macrophages. During the early stages of the inflammatory response, they suppress TNF-alpha release via induction of COX-2/PGE2 while later on they induce TNF-alpha transcription. Hence, the reported anti-inflammatory effect of CRF-peptides appears to involve macrophages and is confined at the early stage of inflammation.
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PMID:Corticotropin releasing factor receptor 1 (CRF1) and CRF2 agonists exert an anti-inflammatory effect during the early phase of inflammation suppressing LPS-induced TNF-alpha release from macrophages via induction of COX-2 and PGE2. 1711 78

The association between inflammation and neuropsychiatric symptoms in old age is generally accepted but poorly understood. The purpose of this study was to examine whether inflammation precedes depressive symptoms and cognitive decline in old age, and to identify specific inflammatory pathways herein. We measured serum C-reactive protein (CRP) and lipopolysaccharide-induced production of Interleukin (IL)-1beta, IL-6, Tumor Necrosis Factor (TNF)-alpha, IL-1 receptor antagonist (ra), and IL-10 levels in 85-year-old participants free from neuropsychiatric symptoms at baseline (n=267). Participants were prospectively followed for depressive symptoms (Geriatric Depression Scale) and cognitive functioning (Mini Mental State Examination) from 85 to 90 years. Higher baseline CRP levels preceded accelerated increase in depressive symptoms (p<0.001). A higher production capacity of the pro-inflammatory cytokine IL-1beta preceded a greater increase of depressive symptoms (p=0.06), whereas that of its natural antagonist IL-1ra preceded a smaller increase of depressive symptoms (p=0.003). There was no relation of CRP, IL-1beta, and IL-1ra with cognitive decline. Our findings show that in old age inflammatory processes contribute to the development of depressive symptoms but not cognitive decline. A high innate IL-1ra to IL-1beta production capacity reflects a better ability to neutralize inflammation and may therefore protect against depressive symptoms.
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PMID:Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. 1735 Jul 81

The pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNFalpha) and Interleukin-1 (IL-1) mediate the innate immune response. Dysregulation of the innate immune response contributes to the pathogenesis of cancer, arthritis, and congestive heart failure. TNFalpha- and IL-1-induced changes in gene expression are mediated by similar transcription factors; however, TNFalpha and IL-1 receptor knock-out mice differ in their sensitivities to a known initiator (lipopolysaccharide, LPS) of the innate immune response. The contrasting responses to LPS indicate that TNFalpha and IL-1 regulate different processes. A large-scale proteomic analysis of TNFalpha- and IL-1-induced responses was undertaken to identify processes uniquely regulated by TNFalpha and IL-1. When combined with genomic studies, our results indicate that TNFalpha, but not IL-1, mediates cell cycle arrest.
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PMID:Tumor Necrosis Factor-alpha- and interleukin-1-induced cellular responses: coupling proteomic and genomic information. 1750 96

Vertebrates harbor abundant lipopolysaccharide (LPS) in their gut microbiota. Alkaline phosphatases can dephosphorylate and detoxify the endotoxin component of LPS. Here, we show that expression of the zebrafish intestinal alkaline phosphatase (Iap), localized to the intestinal lumen brush border, is induced during establishment of the gut microbiota. Iap-deficient zebrafish are hypersensitive to LPS toxicity and exhibit the excessive intestinal neutrophil influx characteristic of wild-type zebrafish exposed to LPS. Both of these Iap mutant phenotypes are dependent on Myd88 and Tumor Necrosis Factor Receptor (Tnfr), proteins also involved in LPS sensitivity in mammals. When reared germ-free, the intestines of Iap-deficient zebrafish are devoid of neutrophils. Together, these findings demonstrate that the endogenous microbiota establish the normal homeostatic level of neutrophils in the zebrafish intestine through a process involving Iap, Myd88, and Tnfr. Thus, by preventing inflammatory responses, Iap plays a crucial role in promoting mucosal tolerance to resident gut bacteria.
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PMID:Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. 1807 87

Innate propensity of immune activation is reflected in production of pro- and anti-inflammatory cytokines upon stimulation of Toll-like receptors (TLR) in whole-blood stimulation assays. The validity of the whole-blood stimulation assay under field conditions has not been evaluated extensively. Here, we have determined correlation of individually repeated whole-blood stimulation assays in a field-study in Ghana and compared it with that of two Dutch populations performed under optimal conditions. We also examined cytokine production to various TLR-agonists in order to create an assay that would mimic general innate immune responses. Under field conditions repeated assessments of lipopolysaccharide-induced Tumor Necrosis Factor-alpha (TNFalpha) production were poorly correlated (r=0.15, p=0.087). Correlation was relatively high for production of Interleukin-10 (IL10) (r=0.48, p<0.001) and comparable to that observed in the Dutch population under optimal conditions. Combined stimulation with lipopolysaccharide and zymosan resulted in cytokine production profiles that were similar to that attained after stimulation with a mixed culture of bacteria. Here, we conclude that variation of a whole-blood assay performed in field setting is large in general but that production of IL10 seems to better reflect an innate pro- or anti-inflammatory tendency whereas production of TNFalpha may predominantly reflect recent immunological challenges. Furthermore, simultaneous stimulation of several Toll-like receptors may mimic general innate immune activation.
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PMID:Performance of the whole-blood stimulation assay for assessing innate immune activation under field conditions. 1918 6


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