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)

Muscle growth in meat animals is a complex process governed by integrated signals emanating from multiple endocrine and immune cells. A generalized phenomenon among meat animal industries is that animals commonly fail to meet their genetic potential for growth in commercial production settings. Therefore, understanding the impact of stress and disease on muscle growth is essential to improving production efficiency. The adipocyte in particular seems to be well positioned as an interface between energy status and immune function, and may thus influence nutrient partitioning and growth through a combination of signals that influence fat metabolism, glucose uptake, and insulin sensitivity. Adipocytes and myofibers are active participants in the innate immune response, and as such, produce a number of metabolic regulators, including leptin, adiponectin, and proinflammatory cytokines. Specifically, adipocytes and muscle cells respond directly to bacterial lipopolysaccharide (LPS) by producing interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha). However, adipocytes are also the predominant source of the antiinflammatory hormone adiponectin, which regulates the nuclear factor kappa-B transcription factor. The ability to recognize antigens and produce regulatory molecules strategically positions adipocytes and myofibers to regulate growth locally, and to reciprocally regulate metabolism peripherally.
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PMID:Adipocytes, myofibers, and cytokine biology: new horizons in the regulation of growth and body composition. 1658 86

The blood-brain barrier (BBB) prevents the unrestricted movement of peptides and proteins between the brain and blood. However, some peptides and regulatory proteins can cross the BBB by saturable and non-saturable mechanisms. Leptin and insulin each cross the BBB by their own transporters. Impaired transport of leptin occurs in obesity and accounts for peripheral resistance; that is, the condition wherein an obese animal loses weight when given leptin directly into the brain but not when given leptin peripherally. Leptin transport is also inhibited in starvation and by hypertriglyceridemia. Since hypertriglyceridemia occurs in both starvation and obesity, we have postulated that the peripheral resistance induced by hypertriglyceridemia may have evolved as an adaptive mechanism in response to starvation. Insulin transport is also regulated. For example, treatment of mice with lipopolysaccharide (LPS) increases insulin transport across the BBB by about threefold. Since many of the actions of CNS insulin oppose those of peripheral insulin and since LPS releases proinflammatory cytokines, enhanced transport of insulin across the BBB could be a mechanism which promotes insulin resistance in sepsis. The brain endothelial cells which comprise the BBB secrete many substances including cytokines. Such secretion can be stimulated from one side of the BBB with release into the other side. For example, it appears that adiponectin can inhibit release of interleukin-6 from brain endothelial cells. Overall, the BBB represents an important interface in mediating gut-brain axes.
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PMID:The blood-brain barrier as a regulatory interface in the gut-brain axes. 1690 39

There is a growing appreciation that adipose tissue is a multifunctional organ. In addition to its central role in lipid storage, adipose tissue secretes a diverse group of proteins, called adipokines, involved in lipid metabolism, insulin sensitivity, angiogenesis etc. Adipocytes also secrete various inflammatory and anti-inflammatory mediators. Adiponectin, an adipokine with potent anti-inflammatory properties, is thought to play an important role in the regulation of inflammation. The development of alcoholic liver disease is thought to involve increased pro-inflammatory activity, mediated in part by the activation of Kupffer cells. Chronic ethanol feeding sensitizes Kupffer cells to activation by lipopolysaccharide (LPS), leading to increased production of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha). Recent studies have demonstrated a hepato-protective effect of adiponectin in the progression of alcoholic liver disease. Herein are summarized recent data demonstrating that adiponectin treatment can normalize LPS-stimulated ROS production and TNF-alpha expression in Kupffer cells after chronic ethanol feeding. These studies suggest that the hepato-protective activity of adiponectin is due, at least in part, to a direct anti-inflammatory effect of adiponectin on Kupffer cells.
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PMID:Regulation of Kupffer cell activity during chronic ethanol exposure: role of adiponectin. 1695 68

The blood-brain barrier (BBB) plays a critical role in the transduction of signals between the central nervous system and peripheral tissues. It does so through several mechanisms, including the direct transport of peptides and regulatory proteins such as insulin and leptin. Another mechanism that may be important is the secretion by brain endothelial cells of substances that affect feeding, such as proinflammatory cytokines and NO. We have recently shown that the BBB is capable of receiving an input from one side and secreting a substance into the other. Additionally, BBB secretions can be modulated by substances that affect feeding, such as adiponectin and lipopolysaccharide.
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PMID:Blood-brain barrier and energy balance. 1702 73

Previous epidemiologic studies have suggested that periodontal disease is closely related to obesity and glucose tolerance. As the level of adiponectin, an adipocyte-derived cytokine, in plasma had been reported to decrease in obese and type 2 diabetes patients, we explored the role of adiponectin in the etiology of periodontitis using the D clone of RAW264, a clone that exhibits highly efficient osteoclast formation, to determine whether adiponectin acts as a regulatory molecule in osteoclast formation stimulated by lipopolysaccharide of periodontopathic bacteria. We observed that adiponectin acted as a potent inhibitor of osteoclast formation stimulated by Toll-like receptor 4 (TLR4) ligand and receptor activator of NF-kappaB ligand (RANKL). Because NF-kappaB is an important transcription factor in osteoclast formation, we examined the effect of adiponectin on its transcriptional activity. A luciferase assay showed that adiponectin was able to inhibit the TLR4-mediated NF-kappaB activity in RAW264 cells. In addition, we observed that the cytokine was actually able to inhibit TLR4-mediated expression of the gene for inducible nitric oxide synthase and production of nitric oxide in the cells. These observations strongly suggest that adiponectin may function as a negative regulator of lipopolysaccharide/RANKL-mediated osteoclast formation in periodontal disease.
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PMID:Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Actinobacillus actinomycetemcomitans. 1709 90

Several recently published reports, including ours, suggest that adiponectin is a strong proinflammatory agent. Indeed, exposure of human placenta and adipose tissue to adiponectin induces the production of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). We have previously shown that adiponectin is a powerful inducer of proinflammatory cytokines production by macrophages. The reported anti-inflammatory effect of adiponectin may be due to the induction of macrophage tolerance to further adiponectin exposure or to other proinflammatory stimuli including the Toll-like receptor (TLR) 3 ligand polyI:C and the TLR4 ligand lipopolysaccharide (LPS). We now present additional data supporting the hypothesis that adiponectin is a strong proinflammatory adipokine. More specifically, we demonstrate that adiponectin induces IL-1beta and IL-8 from THP-1 macrophage cell line. The effect of adiponectin is not restricted to differentiated THP-1 macrophages but it is evident at lower levels in undifferentiated THP-1 monocytes promoting TNF-alpha, IL-6, and IL-8 production. Thus, its high levels in the circulation of lean subjects render their macrophages resistant to several proinflammatory stimuli including its own thus acting in effect as an anti-inflammatory agent. Lowering of its high levels, as a consequence of increased body mass index (BMI), renders macrophages sensitive to any proinflammatory insult.
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PMID:Peripheral factors in the metabolic syndrome: the pivotal role of adiponectin. 1714 40

Recent reports suggest the potential role of toll-like receptor 4 (TLR4) in initiation of inflammatory responses and fatty acid-induced insulin resistance. We describe here the synthesis of pro-inflammatory products in 3T3-L1 preadipocyte cell line after stimulation with lipopolysaccharide (LPS), a TLR4 agonist. Expression profiles of mRNA coding for IL6, CCL2, CCL5, CCL11, NOS2, and PTGS2 demonstrated a higher responsiveness to LPS of these transcripts in preadipocytes than in fully differentiated adipocytes, confirming inflammatory features of preadipocytes. IL6, CCL2, CCL5 and CCL11 were secreted in 3T3-L1 supernatants within 4 h after LPS stimulation. In addition, continuous exposure to LPS during adipocyte differentiation impaired this process as was demonstrated by analysis of mRNA profiles of lipogenesis enzymes (FABP4, GPD1, LPL), adipokines (adiponectin, resistin, visfatin, leptin), and of the transcription factor PPARgamma. This suggests that toll-like receptor mediated activation could regulate maintenance of preadipocyte status, and inflammatory environment encountered in inflamed white adipose tissue.
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PMID:Preadipocyte response and impairment of differentiation in an inflammatory environment. 1738 12

Adiponectin is an adipokine with potent anti-inflammatory properties. However, the mechanisms by which adiponectin suppresses macrophage function are not well understood. Treatment of RAW264.7 macrophages with adiponectin for 18 h decreased lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) production. Here we demonstrate that globular adiponectin (gAcrp) initially increased TNF-alpha expression in RAW264.7 macrophages; this TNF-alpha then contributed to increased expression of interleukin-10, which in turn was required for the development of tolerance to subsequent LPS exposure. gAcrp-mediated increases in TNF-alpha mRNA accumulation were associated with increased TNF-alpha promoter activity. gAcrp increased the DNA binding activity of both Egr-1 and NFkappaB; mutation of either the Egr-1 or NFkappaB binding sites in the TNF-alpha promoter decreased gAcrp-stimulated promoter activity. Further, co-transfection with either dominant negative Egr-1 or the IkappaB super-repressor prevented gAcrp-stimulated TNF-alpha promoter activity. gAcrp also increased Egr-1 promoter activity, mRNA accumulation, and DNA binding activity. Inhibition of ERK1/2 with U0126 potently suppressed gAcrp-stimulated Egr-1 promoter activity, as well as TNF-alpha promoter activity. In summary, these data demonstrate that adiponectin initially increases TNF-alpha production by macrophages via ERK1/2-->Egr-1 and NFkappaB-dependent mechanisms; these increases in TNF-alpha in turn lead to increased expression of interleukin-10 and an eventual dampening of LPS-mediated cytokine production in macrophages.
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PMID:Short-term treatment of RAW264.7 macrophages with adiponectin increases tumor necrosis factor-alpha (TNF-alpha) expression via ERK1/2 activation and Egr-1 expression: role of TNF-alpha in adiponectin-stimulated interleukin-10 production. 1753 27

In order to investigate the effects of simvastatin on secretion and mRNA expression of interleukin-6 (IL-6) and adiponectin in 3T3-L1 adipocytes, mouse 3T3-L1 adipocytes were stimulated with lipopolysaccharide (LPS). Production and mRNA expression of IL-6 and adiponectin in 3T3-L1 adipocytes were measured using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The results showed that simvastatin could significantly suppress LPS-induced IL-6 production and mRNA expression in adipocytes (P<0.05), but increase the LPS-induced adiponectin secretion and mRNA expression in a dose-dependent manner (P<0.05). It was suggested that simvastatin could exert beneficial effects on prevention of obesity-induced metabolic changes in adipocytes.
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PMID:Effect of simvastatin on IL-6 and adiponectin secretion and mRNA expression in 3T3-L1 adipocytes. 1764 34

Adipose tissue secretes a wide range of hormones named adipokines, and these may play a role in obesity-related inflammation. Adiponectin is an exceptional adipokine because low plasma concentrations are associated with obesity, type 2 diabetes, and cardiovascular diseases. It has been observed that plasma adiponectin concentrations are elevated during inflammatory conditions like preeclampsia and arthritis. Nuclear factor-kappaB (NF-kappaB) is an essential transcription factor for expression of inflammation-related proteins. We have used U937 cells stably transfected to express luciferase under the control of NF-kappaB to examine if adiponectin may modulate NF-kappaB activity. Physiological concentrations of native adiponectin induced NF-kappaB activity. This effect was relatively strong compared with proinflammatory adipokines like leptin, resistin, and IL-6. The enhanced NF-kappaB activity was attributed to the high molecular weight adiponectin isoforms. NF-kappaB was not activated by mutated adiponectin that is unable to form high molecular weight complexes. Furthermore, the C-terminal fragment, globular adiponectin, markedly increased NF-kappaB reporter activity, cytokine release, and mRNA expression of inflammation marker genes, at higher levels than stimulation with TNF-alpha and lipopolysaccharide. NF-kappaB activation by globular adiponectin was not affected by antibody inhibition of toll-like receptor 4 or TNF receptors 1 and 2 but was attenuated by inhibitors of p38 MAPK, phosphatidylinositol 3-kinase, and protein kinase C. Analyses of the p65 subunit of NF-kappaB in different leukocyte cell lines showed activation of two monocytic cell lines (U937 and THP-1) by native and globular adiponectin. Our results indicate that adiponectin has proinflammatory properties in monocytic cells.
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PMID:Activation of nuclear factor-kappaB by high molecular weight and globular adiponectin. 1770 46


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