Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sodium iodide symporter (NIS), first identified in FRTL-5 cells, plays a critical role in iodide transport in the thyroid gland and in the production of the iodine-containing thyroid hormones. The aim of our study was to examine the regulation of NIS RNA steady-state levels and protein expression as well as functional activity in FRTL-5 cells. FRTL-5 cells cycling in media containing thyrotropin (TSH) were incubated for 48 hours with dexamethasone (10(-8)-10(-5) M), triiodothyronine (T3; 10(-9)-10(-6) M), methimazole (100 microM), propylthiouracil (PTU; 100 microM), perchlorate (10 microM) and potassium iodide (40 microM). In other experiments, cells were treated for 48 hours with various cytokines including interleukin-6 (IL-6) (100 U/mL), interferon-gamma (IFN-gamma) (100 U/mL), tumor necrosis factor-alpha (TNF-alpha) (10 ng/ml), IL-1alpha (100 U/mL), and IL-1beta (100 U/mL). Northern blot analysis using a 32P-labeled rat NIS-specific cDNA probe (nucleotides 1397-1937) revealed NIS mRNA as a single species of approximately 3 kb. When normalized for beta-actin mRNA signal intensities, NIS RNA steady-state levels in viable FRTL-5 cells were suppressed by approximately 80% after incubation with dexamethasone and T3 in a concentration-dependent manner. Iodide accumulation was decreased by up to 40% after incubation with dexamethasone and T3, respectively, in a concentration-dependent manner. Using a rabbit polyclonal rNIS-specific antibody, Western blot analysis of FRTL-5 cell membranes revealed a 60% and 70% suppression of NIS protein expression after treatment with T3 (0.1 microM) and dexamethasone (1 microM), respectively. In additon, NIS RNA steady-state levels were decreased by approximately 50% after treatment of monolayers with methimazole, PTU, and potassium iodide, respectively. Incubation with methimazole and PTU resulted in a 20% and 25% decrease of iodide accumulation, respectively, whereas potassium iodide suppressed iodide accumulation by approximately 50%. Treatment of FRTL-5 cells with IL-6 and IL-1beta resulted in a 30% decrease of NIS RNA steady-state levels. IL-6 did not alter NIS functional activity, but IL-1beta suppressed iodide accumulation by approximately 25%. IFN-gamma and perchlorate failed to alter NIS RNA steady-state levels. In contrast to IFN-gamma that had no effect on iodide accumulation, perchlorate almost completely suppressed iodide accumulation. TNF-alpha and IL-1alpha failed to alter NIS RNA steady-state levels in higher passage numbers of FRTL-5 cells, whereas treatment with TNF-alpha and IL-1alpha of early passages of FRTL-5 cells (<20 cell passages) resulted in a 70% and 40% decrease of NIS RNA steady-state levels, respectively, and in a 20% suppression of NIS functional activity. In conclusion, our data suggest that various agents known to affect iodide transport are capable of differentially altering NIS gene expression and function in cultured thyroid cells. Suppression of NIS gene expression and function by certain cytokines may be responsible, at least in part, for the impaired radioiodine uptake by thyroid tissue in certain forms of thyroiditis.
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PMID:Regulation of sodium iodide symporter gene expression in FRTL-5 rat thyroid cells. 1048 76

To investigate whether the results of intratracheal instillation studies on mineral fibers reflect the findings obtained by long-term inhalation data on mineral fibers, we have examined gene expression of cytokines and pathological features in lungs induced by intratracheal instillation and inhalation of mineral fibers. Male Wistar rats were given a single intratracheal instillation of 2 mg alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (PT1), and were sacrificed 4 wk after the fiber instillation. Long-term inhalation studies were also performed. In these, animals were exposed to fiber aerosol of RF1 or PT1 for 5 days/wk for 1 yr, and sacrificed after 1 yr of inhalation. Expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1) from lungs was observed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of TNF-alpha, IL-6, and TGF-beta1 mRNA in PT1-exposed lung was significantly higher than for those exposed to RF1 in both intratracheal instillation and inhalation studies. Pathological findings revealed that mild pulmonary fibrosis was seen in the lungs after intratracheal instillation and inhalation of PT1 but not RF1. Similarities were observed not only in gene expression of cytokines but in pathological features between both studies. These data suggested that the results of intratracheal instillation reflect the findings obtained from long-term inhalation data.
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PMID:Comparison of gene expression of cytokines mRNA in lungs of rats induced by intratracheal instillation and inhalation of mineral fibers. 1145 56

A prospective study was done to determine the changes in blood quality parameters of collected drainage blood in retransfusion systems at 6 and 12 h after surgery to verify whether the blood was still suitable for retransfusion purposes for an additional 6 postoperative hours beyond the so far accepted first 6-h time window after surgery. Eighty-one patients received retransfusion within the first 6 h immediately following total knee arthroplasty. Additionally, drainage blood was collected for another 6 h using the same retransfusion system. Samples for laboratory analysis were taken from both the first and second 6-h blood collection interval. Hemoglobin values increased from 9.6 to 10.4 g dl(-1) (p = 0.021). Platelet counts increased from 65,500 to 80,900 microl(-1) (p < 0.001). Leukocyte counts increased from 5,550 to 8,190 1(-1) (p < 0.001). Lactate dehydrogenase (672 U l(-1) during the first vs 651 U l(-1) during the second collection period) and free hemoglobin (71.7 mg dl(-1) vs 67.0 mg dl(-1)) did not change significantly. The potassium concentration decreased slightly from 4.33 to 4.20 mg dl(-1) (p = 0.002). The lactate concentration increased from 4.44 to 7.21 mg dl(-1) (p < 0.001). The pH decreased from 7.07 to 6.94 (p < 0.001). Interleukin-6 concentration increased from 6,500 to 46,500 ng l(-1) (p < 0.001). In this study, we found no relevant difference in most of the drainage blood quality parameters between the first 6-h collection period and the second 6-h collection with regard to its suitability for autologous retransfusion except higher interleukin-6 levels. Due to the higher interleukin concentration, a possible increase in febrile reactions should be taken into account during retransfusion.
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PMID:Time-related changes of collected shed blood in autologous retransfusion after total knee arthroplasty. 1176 35

The influence of acid-citrate-dextrose (ACD) anticoagulant on the blood quality was assessed in this prospective, randomized, controlled study. The clinical consequences with regard to retransfusion of drainage blood following total knee arthroplasty were evaluated. After total knee arthroplasty, retransfusion was performed utilizing a "SureTrans" retransfusion system in 81 patients. In 42 of them, blood was collected adding an ACD anticoagulant (group A), while in the remaining 39 patients blood was collected without any additives (group B). Blood losses were retransfused over a 6-h period after attaching the retransfusion system to the patient of either group. Blood samples of the 6-h blood collection were taken and analysed for several blood quality parameters. Significant differences were found in the platelet count (61,200+/-16,700 microl(-1) in group A versus 70,100+/-21,600 microl(-1) in group B, p=0.042), the lactate concentration (4.09+/-0.86 mmol/l vs 4.82+/-0.83 mmol/l, p<0.001), the pH (6.96+/-0.10 vs 7.18+/-0.06, p<0.001), as well as the protein content (5.44+/-0.57 g/dl vs 5.85+/-0.43 g/dl, p<0.001). These observed significant differences were, however, of no clinical relevance to the patients' treatment. Hemoglobin concentration, hematocrit, mean corpuscular volume (MCV), erythrocyte count, leukocyte count, concentration of free hemoglobin in the blood plasma (fHb), potassium concentration, lactate dehydrogenase (LDH), serotonin concentration, triglyceride concentration, free fatty acid concentration, and interleukin-6 concentration did not differ significantly. This study indicates that the blood quality in retransfusion systems is not substantially influenced by adding ACD anticoagulant.
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PMID:Influence of acid-citrate-dextrose anticoagulant on blood quality in retransfusion systems after total knee arthroplasty. 1207 Jun 45

The plant amino acid L-mimosine has recently been suggested to inhibit cells at a regulatory step in late G1 phase before establishment of active DNA replication forks. In addition, L-mimosine is an extremely effective inhibitor of DNA replication in chromosomes of mammalian nuclei. In this work, the effect of L-mimosine on chronic inflammation induced by dorsal injections of 0.2 ml of a 1:40 saturated crystal solution of potassium permanganate in mice, was studied. Seven days afterwards, all mice developed a subcutaneous granulomatous tissue indicative of chronic inflammatory response at the site of infection. The intraperitoneal administration of L-mimosine (200 microg/dose) to the potassium permanganate treated mice for 5 consecutive days (the first at the same time of inoculation of the KMnO4), produced a significant decrease in size and weight of the granuloma when compared to mice not treated with L-mimosine (controls). In addition, in all mice treated with L-mimosine, there was a strong inhibition of tumor necrosis factor alpha that was revealed in the serum (P<0.05) and in the minced granulomas. Interleukin-6 was not detected in the serum of treated and untreated mice. These findings show for the first time, that L-mimosine may have an anti-inflammatory effect on chronic inflammation and an inhibitory effect on tumor necrosis factor alpha and interleukin-6 generation in supernatant fluids of minced granulomas.
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PMID:Effect of the compound L-mimosine in an in vivo model of chronic granuloma formation induced by potassium permanganate (KMNO4). 1279 99

This review discusses the myocardial protective property of the insulin/glucose-insulin-potassium regimen and the mechanisms involved in this beneficial action. Several recent studies suggest that insulin not only is useful to control hyperglycemia and maintain glucose homeostasis but also may have the unique property to protect the myocardium from reperfusion injury and ischemia and prevent apoptosis of myocardial cells. The insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha, interleukin-6, macrophage migration inhibitory factor and other pro-inflammatory cytokines, and free radicals; and enhances the synthesis of endothelial nitric oxide and anti-inflammatory cytokines interleukin-4 and interleukin-10. Thus, the insulin/GIK regimen brings about its cardioprotective action. This may also explain why the insulin/GIK regimen is useful in sepsis and septic shock, myocardial recovery in acute myocardial infarction, and critical illness. It is suggested that the infusion of adequate amounts of insulin to patients with acute myocardial infarction, congestive heart failure, cardiogenic shock, and critical illness preserves myocardial integrity and function and ensures rapid recovery. In view of the suppressive action of insulin on the synthesis of proinflammatory cytokines and free radicals, it is possible that the insulin/GIK regimen, when used in a timely and appropriate fashion, may also protect other tissues and organs and facilitate in the recovery of patients who are critically ill.
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PMID:Insulin: an endogenous cardioprotector. 1450 50

The mechanisms behind the development of work-related trapezius pain are suggested to involve both peripheral and central components, but the specific contribution of alterations in muscle nociceptive and other substances is not clear. Female patients with chronic trapezius myalgia (N=19; TM) and female controls (N=20; CON) were studied at rest, during 20 min repetitive low-force exercise and recovery, and had their interstitial concentrations of potassium (K(+)), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and collagen turnover determined in the trapezius muscle by the microdialysis technique. K(+) levels were at all time points higher in TM than in CON (P<0.0001). Baseline levels of LDH and IL-6 were similar in both groups. In response to exercise pain intensity, rated perceived exertion, and the concentrations of K(+), LDH and IL-6 increased significantly in both groups. [K(+)] immediately decreased to baseline levels in CON but remained elevated during the first 20 min of recovery in TM (P<0.01) whereafter it returned to baseline level. In all subjects taken together mean [K(+)] correlated negatively with pressure pain threshold of trapezius (P<0.001), positively with mean pain intensity VAS (P<0.001) and mean perceived exertion (P<0.001). Rises in muscle LDH and IL-6 as well as the anabolic ratio for collagen type I was not significantly different between groups. In conclusion, patients with chronic pain in the trapezius muscle had increased levels of interstitial potassium. This finding could be causally related to myalgia or secondary to pain due to deconditioned muscle or altered muscle activity pattern.
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PMID:Increased levels of interstitial potassium but normal levels of muscle IL-6 and LDH in patients with trapezius myalgia. 1629 53

Pyruvic acid, an intermediate metabolite of glucose, an effective scavenger of reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production and NF-kappaB signaling pathways, reduces circulating levels of HMGB1 (high mobility group B1), decreases COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa, and colonic mucosa in animal models with endotoxemia. These studies suggest that pyruvate has potent anti-oxidant and anti-inflammatory actions. Insulin influences the production of pyruvate by its action on glucose metabolism and pyruvate is an insulin secretagogue. This suggests that in metabolic syndrome X, obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is common due to enhanced TNF-alpha production) pyruvate plays a role. This may have relevance to the use of glucose-insulin-potassium regimen in these clinical conditions, sepsis, and cancer.
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PMID:Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. 1664 87

Ketamine is the only intravenous anesthetic that causes an increase in mean arterial pressure without compromising cardiac output. These beneficial effects are basically linked to stimulation of the sympathetic nervous system, inhibition of adenosine triphosphate-sensitive potassium channels and interactions with the nitric oxide pathway. Experimental and clinical studies have shown that ketamine exerts antiinflammatory properties by inhibiting the release of proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6. In addition, there is increasing evidence that early ketamine administration reduces mortality in experimental sepsis models. In view of the current literature ketamine appears to represent a beneficial therapeutic option for long-term sedation of patients with arterial hypotension resulting from sepsis and systemic inflammatory response syndrome (SIRS). However, it has to be taken into account that ketamine inhibits endothelial nitric oxide synthase, thereby potentially aggravating impaired (micro) regional blood flow in sepsis. Future studies are required to investigate the role of ketamine in the treatment of patients with sepsis and SIRS.
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PMID:[Role of ketamine in sepsis and systemic inflammatory response syndrome]. 1677 27

Cytokines are emerging as important in developmental processes. They may induce alterations in normal gene expression patterns, activate angiotensinogen transcription, or alter expression of the renin-angiotensin system (RAS). To determine whether prenatal exposure to interleukin-6 (IL-6) influences gene expression of the intrarenal RAS and contributes to renal dysfunction and hypertension in adulthood, we exposed female rats to IL-6 early (EIL-6 females) and late (LIL-6 females) in pregnancy and analysed blood pressure in the offspring at 5-20 weeks of age. Renal fluid and electrolyte excretion was assessed in clearance experiments, mRNA expression by real-time PCR, and protein levels by Western blot. Systolic pressure was increased at 5 weeks in IL-6 females and at 11 weeks in males. Circulatory RAS levels were increased in all IL-6 females, but angiotensin-1-converting enzyme (ACE) activity was increased only in LIL-6 females. LIL-6 males and IL-6 females showed decreased urinary flow rate and urinary sodium and potassium excretion. Dopamine excretion was decreased IL-6 females. In adult renal cortex, renin expression was increased in all IL-6 females, but angiotensinogen mRNA was increased only in LIL-6 females; AT(1) receptor (AT(1)-R) mRNA and protein levels were increased in LIL-6 females, whereas AT(2) receptor (AT(2)-R) levels were decreased in LIL-6 females and EIL-6 males. In adult renal medulla, AT(1)-R protein levels were increased in LIL-6 females, and AT(2)-R mRNA and protein levels were decreased in EIL-6 males and LIL-6 females. Prenatal IL-6 exposure may cause hypertension by altering the renal and circulatory RAS and renal fluid and electrolyte excretion, especially in females.
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PMID:Prenatal exposure to interleukin-6 results in hypertension and alterations in the renin-angiotensin system of the rat. 1682 9


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