UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is desirable in the treatment of IgA nephropathy (IgAN) to prevent the downstream events after the immune response has involved the glomerulus. We and others observed that IgA itself could directly activate mesangial cells to produce monocyte chemotactic peptide-1 (MCP-1), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) and this was suppressed by the treatment with steroid or angiotensin receptor blocker (ARB). It was shown in mesangial cells that the increased expression of TGF-beta and plasminogen activator inhibitor-1 induced by angiotensin II was suppressed by the treatment with ARB, calcium channel blocker (CCB), spironolactone or peroxisome proliferator-activated-receptor-gamma (PPAR-gamma) agonist. It was well known in the patients with IgAN that renal or intraglomerular TGF-beta1 gene expression was increased. Interestingly, treatment with angiotensin-converting enzyme (ACE) inhibitors induced significantly lower renal TGF-beta1 gene expression in patients with IgAN. It was reported in several studies that urinary levels of IL-6, IL-8, MCP-1 or TGF-beta were increased in patients with IgAN. The increase was suppressed by the treatment with steroid, ARB or ACE inhibitor. More effective agents are necessary to ameliorate pathogenetic abnormalities and so to prevent the progression of IgAN.
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PMID:Effects of therapeutic agents on the inflammatory and fibrogenic factors in IgA nephropathy. 1799 24

Hypertension contributes to the occurrence and progression of cardiovascular diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to activate the peroxisome proliferator-activated receptor gamma and improve insulin sensitivity. We investigated the effects of telmisartan treatment on visceral fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive patients. This was an open-label, non-controlled study. Twenty-eight essential hypertensive patients (22 men and 6 women; age 60.6+/-1.9 years; body mass index [BMI] 25.5+/-0.6 kg/m(2)) participated. Fat area was assessed with computerized tomography. All the subjects were started on telmisartan 40 mg/day, which was increased to 80 mg/day to achieve the blood pressure target of less than 130/80 mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan treatment. There were significant reductions in visceral fat area (from 103.1+/-7.9 to 93.3+/-8.4 cm(2), p<0.01) and pulse wave velocity (from 1,706+/-52 to 1,587+/-51 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum high-density lipoprotein cholesterol (from 5.06+/-0.15 to 5.32+/-0.13 mmol/L, p<0.05) and adiponectin levels (from 8.27+/-0.76 to 9.13+/-0.81 microg/mL, p<0.05) were observed. Also, there were reductions in the interleukin-6 level (from 2.26+/-0.27 to 1.60+/-0.14 pg/mL, p<0.01). We also conducted these investigations in male subjects alone and similar findings were obtained for all of these parameters. In conclusion, telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin.
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PMID:Telmisartan treatment decreases visceral fat accumulation and improves serum levels of adiponectin and vascular inflammation markers in Japanese hypertensive patients. 1834 26

Endothelial cells have been shown to induce adrenal steroidogenesis and to enhance aldosterone secretion via angiotensin II and endothelin 1-independent mechanisms. It has been demonstrated that endothelial cells and adrenocortical cells are capable of producing interleukin-6 (IL-6) and IL-6 is a factor known to stimulate adrenal cortisol secretion. We therefore asked whether endothelial cells have an effect on adrenal IL-6 generation and whether IL-6 mediates biosynthesis of aldosterone as is observed after exposure of adrenocortical cells to endothelial cell-conditioned medium (ECCM). Cells from the adrenocortical cancer cell line NCI-H295R were incubated with ECCM produced from human umbilical vein endothelial cells at increasing concentrations. As detected by an enzyme-linked immunosorbent assay, pure ECCM significantly increased IL-6 protein secretion by cultured adrenocortical cells in a dose-dependent fashion, to a 18.0+/-2.0 pg/mL (mean+/-SEM). This was paralleled by an enhanced IL-6 promoter activity as determined with the transfection of an IL-6-promoter-luciferase reporter gene construct. Pure ECCM also induced aldosterone secretion by adrenocortical cells more than three times that of controls with serum-free medium. ECCM PER SE contains significant amounts of IL-6 protein. However, blockade of IL-6 signal transduction did not interfere with aldosterone synthesis. These data suggest that endothelial cells secrete IL-6 and that endothelial cell-derived factors regulate adrenal IL-6 synthesis which does not alter adrenal aldosterone secretion. Our findings support the hypothesis that the endothelium and the adrenal gland may play a role in the development of some forms of hypertension and - more speculative - inflammation.
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PMID:The endothelium secretes interleukin-6 (IL-6) and induces IL-6 and aldosterone generation by adrenocortical cells. 1877 60

The stress and inflammatory responses to burn injury are associated with bone loss. The stress response entails production of large amounts of endogenous glucocorticoids that decrease osteoblasts on the mineralization surface of bone and decreases differentiation of marrow stromal cells into osteoblasts, thereby decreasing the amount of bone formation. Deficiency of osteoblasts also blocks osteoclastogenesis thus leading to low bone turnover and bone loss. The inflammatory response generates cytokines such as interleukin 1-beta and interleukin-6, which normally increase osteoclastogenic bone resorption via stimulation of osteoblast production of RANK ligand. However, in the absence of osteoblasts as a target we postulate that they attack the parathyroid gland chief cells and up-regulate the calcium-sensing receptor. The consequence of this upregulation is the lowering of the circulating calcium necessary to suppress parathyroid hormone production and the development of hypocalcemia and urinary calcium wasting. It is the parathyroid hormone suppression that causes us to postulate acute deficiency of 1,25-dihydroxyvitamin D and the consequence of this for post-burn metabolism could include derepression of the gene that controls renin production, leading to elevated levels of angiotensin II, which can contribute to insulin resistance, as can vitamin D deficiency itself. Moreover, the skin from burned patients cannot synthesize vitamin D normally. Thus vitamin D supplementation is the only means by which to ensure vitamin D sufficiency for burn victims. The proper requirement for vitamin D in acutely burned patients remains unknown.
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PMID:The interaction between burn injury and vitamin D metabolism and consequences for the patient. 1878 7

Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-gamma. Although peroxisome proliferator-activated receptor-gamma activators have been shown to have an anti-inflammatory effect, such as inhibition of cytokine production, it has not been determined whether telmisartan has such effects. We examined whether telmisartan inhibits expression of interleukin-6 (IL-6), a proinflammatory cytokine, in vascular smooth muscle cells. Telmisartan, but not valsartan, attenuated IL-6 mRNA expression induced by tumor necrosis factor-alpha (TNF-alpha). Telmisartan decreased TNF-alpha-induced IL-6 mRNA and protein expression in a dose-dependent manner. Because suppression of IL-6 mRNA expression was prevented by pretreatment with GW9662, a specific peroxisome proliferator-activated receptor-gamma antagonist, peroxisome proliferator-activated receptor-gamma may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-alpha. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor kappaB and CCAAT/enhancer-binding protein-beta sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-alpha-induced nuclear factor kappaB- and CCAAT/enhancer-binding protein-beta-dependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-alpha-infused mice and IL-6 production from rat aorta stimulated with TNF-alpha ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-alpha in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-alpha and angiotensin II play important roles in atherogenesis through enhancement of vascular inflammation, telmisartan may be beneficial for treatment of not only hypertension but also vascular inflammatory change.
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PMID:Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta. 1928 54

Anti-inflammatory properties may contribute to the pharmacological effects of angiotensin II receptor blockers (ARBs), a leading therapeutic class in the management of hypertension and related cardiovascular and renal diseases. That possibility, supported by consistent evidence from in-vitro and animal studies showing pro-inflammatory properties of angiotensin II, has been evaluated clinically by measuring the effect of ARBs on C-reactive protein and other circulating indices of inflammation (e-selectin, adhesion molecules, interleukin-6, tissue necrosis factor-alpha, monocyte chemoattractant protein-1) of potential clinical relevance, a body of evidence that this paper aims to review.
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PMID:The effect of angiotensin receptor blockers on C-reactive protein and other circulating inflammatory indices in man. 1943 69

The importance of inflammation as a driver of pathology is no longer confined to autoimmune and infectious diseases. In line with convincing experimental data as well as abundant clinical findings the current view of atherosclerosis points to inflammation as a critical regulator of atherosclerotic plaque formation and progression leading to the fatal clinical endpoints myocardial infarction, stroke or sudden cardiac death. The underlying mechanisms have been a matter of intense research during the last decades. In this regard, the interleukin-6 (IL-6) cytokines and their signalling events have been shown to contribute to both, atherosclerotic plaque development and plaque destabilisation via a variety of mechanisms. These involve the release of other pro-inflammatory cytokines, oxidation of lipoproteins by phospholipases, stimulation of acute phase protein secretion, the release of prothrombotic mediators, and the activation of matrix metalloproteinases. Moreover, the formation of reactive oxygen species generated by vascular enzyme systems may play a critical role in the regulation of IL-6 indicating a cross talk between vasoactive substances i.e. angiotensin II or adrenalin and pro-inflammatory cytokines such as IL-6. In this review we will summarise and discuss the underlying molecular and cellular mechanisms how IL-6 as an early and central regulator of inflammation contributes to atherosclerosis and how this knowledge can be integrated into the clinical context.
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PMID:How much is too much? Interleukin-6 and its signalling in atherosclerosis. 1965 71

We have shown that tyrosine kinases and mitogen-activated protein kinases mediate angiotensin II (Ang II) effects in cultured rat astrocytes. In this study, we investigated whether Ang II induces Janus kinase (JAK) 2, signal transducer and activators of transcription (STAT) 3 phosphorylation, and interleukin-6 (IL-6) secretion in cultured brainstem rat astrocytes. Ang II increased JAK2 phosphorylation in a time- and dose-dependent manner. Maximal phosphorylation of 1.7+/-0.4 fold above basal was observed at 15 min with 100 nM Ang II. Losartan (10 microM), an AT(1) receptor blocker, inhibited Ang II-mediated JAK2 phosphorylation, while 10 microM PD123319, an AT(2) receptor blocker, was ineffective. The JAK2 inhibitor, AG490 (50 microM), prevented Ang II JAK2 phosphorylation. Ang II also stimulated STAT3 in a concentration- and time-dependent manner. Maximal phosphorylation of 0.8+/-0.11 above basal was observed at 15 min with 100 nM Ang II. Treatment with AG490 reduced Ang II phosphorylation of STAT3 and Ang II-induced astrocyte growth suggesting that JAK2 is an upstream signal in these Ang II effects. Ang II also stimulated IL-6 secretion from brainstem astrocytes in a concentration- and time-dependent manner. Maximal IL-6 secretion of 0.7+/-0.2 above basal was observed with 100 nM Ang II after 48 h of treatment. Losartan decreased Ang II-induced IL-6 secretion while PD123319 was ineffective. Interestingly, AG490 reduced Ang II-stimulated IL-6 secretion. Our study showed for the first time that Ang II induced JAK2/STAT3 phosphorylation and IL-6 secretion through activation of the Ang II AT(1) receptor in brainstem astrocytes. In addition, Ang II stimulated IL-6 secretion and astrocyte growth through the JAK2 pathway in brainstem astrocytes. These results provide new insights into pro-inflammatory and mitogenic signaling mechanisms of Ang II in astrocytes.
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PMID:Angiotensin II activates JAK2/STAT3 pathway and induces interleukin-6 production in cultured rat brainstem astrocytes. 1974 27

1. Understanding of the regulatory mechanisms of gene expression in the control of blood pressure and fluid volume is a key issue in cardiovascular medicine. Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) signalling antagonizes the physiological and pathophysiological effects mediated by the renin-angiotensin-aldosterone system (RAAS) in the regulation of cardiovascular homeostasis. 2. The targeted-disruption of the Npr1 gene (coding for GC-A/PRA) leads to activation of the cardiac RAAS involved in the hypertrophic remodelling process, which influences cardiac size, expression of pro-inflammatory cytokine genes and the behaviour of various hypertrophy marker genes. The Npr1 gene-knockout (Npr1(-/-)) mice exhibit 35-40 mmHg higher systolic blood pressure and a significantly greater heart weight to bodyweight ratio than wild-type (Npr1(+/+)) mice. 3. The expression of both angiotensin-converting enzyme (ACE) and angiotensin II AT(1a) receptors are significantly increased in hearts from Npr1(-/-) mice compared with hearts from Npr1(+/+) mice. In parallel, the expression of interleukin-6 and tumour necrosis factor-alpha is also markedly increased in hearts from Npr1(-/-) mice. 4. These findings indicate that disruption of NPRA/cGMP signalling leads to augmented expression of the cardiac RAAS in conjunction with pro-inflammatory cytokines in Npr1-null mutant mice, which promotes the development of cardiac hypertrophy and remodelling.
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PMID:Regulation of cardiac angiotensin-converting enzyme and angiotensin AT1 receptor gene expression in Npr1 gene-disrupted mice. 1984 97

Activation of type 1 angiotensin (AT(1)) receptors causes hypertension, leading to progressive kidney injury. AT(1) receptors are expressed on immune cells, and previous studies have identified a role for immune cells in angiotensin II-dependent hypertension. We, therefore, examined the role of AT(1) receptors on immune cells in the pathogenesis of hypertension by generating bone marrow chimeras with wild-type donors or donors lacking AT(1A) receptors (BMKO). The 2 groups had virtually identical blood pressures at baseline, suggesting that AT(1) receptors on immune cells do not make a unique contribution to the determination of baseline blood pressure. By contrast, in response to chronic angiotensin II infusion, the BMKOs had an augmented hypertensive response, suggesting a protective effect of AT(1) receptors on immune cells with respect to blood pressure elevation. The BMKOs had 50% more albuminuria after 4 weeks of angiotensin II-dependent hypertension. Angiotensin II-induced pathological injury to the kidney was similar in the experimental groups. However, there was exaggerated renal expression of the macrophage chemokine monocyte chemoattractant protein 1 in the BMKO group, leading to persistent accumulation of macrophages in the kidney. This enhanced mononuclear cell infiltration into the BMKO kidneys was associated with exaggerated renal expression of the vasoactive mediators interleukin-1beta and interleukin-6. Thus, in angiotensin II-induced hypertension, bone marrow-derived AT(1) receptors limited mononuclear cell accumulation in the kidney and mitigated the chronic hypertensive response, possibly through the regulation of vasoactive cytokines.
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PMID:A role for angiotensin II type 1 receptors on bone marrow-derived cells in the pathogenesis of angiotensin II-dependent hypertension. 2051 91

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