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)

Inhalation of O3 causes airways neutrophilic inflammation accompanied by other changes including increased levels of cyclo-oxygenase products of arachidonic acid in bronchoalveolar lavage fluid (BALF). Ozone O3 exposure also causes decreased forced vital capacity (FVC) and forced expiratory volume after 1 s (FEV(1)), associated with cough and substernal pain on inspiration, and small increases in specific airway resistance (SRAW). The spirometric decrements are substantially blunted by pretreatment with indomethacin. Since the O3-induced decrement in FVC is due to involuntary inhibition of inspiration, a role for stimulation of nociceptive respiratory tract afferents has been suggested and cyclo-oxygenase products have been hypothesized to mediate this stimulation. However, the relation (if any) between the O3-induced neutrophilic airways inflammation and decreased inspiratory capacity remains unclear. We studied the effects of pharmacologic inhibition of O3-induced spirometric changes on the inflammatory changes. Each of ten healthy men was exposed twice (5-week interval) to 0.4 ppm O3 for 2 h, including 1 h of intermittent exercise (ventilation 601*min(-1)). One-and-a-half hours prior to and midway during each exposure the subject ingested 800 mg and 200 mg, respectively, of the non-steroidal anti-inflammatory drug ibuprofen (IBU), or placebo [PLA (sucrose)], in randomized, double-blind fashion. Spirometry and body plethysmography were performed prior to drug administration, and before and after O3 exposure. Immediately following postexposure testing, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed. Neither IBU nor PLA administration changed pre-exposure lung function. O3 exposure (with PLA) caused a significant 17 percent mean decrement in FEV(1) (P <0.01) and a 56 percent increase in mean SRAW. Following IBU pretreatment, O3 exposure induced a significantly lesser mean decrement in FEV(1) (7 percent) but still a 50 percent increase in mean SRAW. IBU pretreatment significantly decreased post-O3 BAL levels of prostaglandin E2 (PGE2) by 60.4 percent (P <0.05) and thromboxane B(2) (TxB(2)) by 25.5 percent (P <0.05). Of the proteins, only interleukin-6 was significantly reduced (45 percent, P <0.05) by IBU as compared to PLA pretreatment. As expected, O3 exposure produced neutrophilia in BALF. There was, however, no effect of IBU on this finding. None of the major cell types in the BALF differed significantly between pretreatments. We found no association between post-exposure changes of BALF components and pulmonary function decrements. We conclude that IBU causes significant inhibition of O3-induced increases in respiratory tract PGE(2) and TxB(2) levels concomitant with a blunting of the spirometric response. This is consistent with the hypothesis that the products of AA metabolism mediate inhibition of inspiration. However, IBU did not alter the modest SRAW response to O3.
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PMID:Effects of cyclo-oxygenase inhibition on ozone-induced respiratory inflammation and lung function changes. 886 65

All previous in vitro biocompatibility tests of peritoneal dialysis fluids have shown that these have inhibitory effects on the function of peritoneal mesothelium. This report presents results from in vitro experiments performed to study the effect of dialysis fluids (Dianeal 1.36 and Dianeal 3.86; Baxter, Round Lake, IL) on the function of mesothelial cells under conditions that simulate the in vivo state of these solutions in the peritoneal cavity. Thus, cells were initially exposed only to the unused fluids that were thereafter gradually diluted (over 4 hours) with pooled effluent dialysate from continuous ambulatory peritoneal dialysis patients. During the following 20 hours, cells were incubated in a mixture of unused fluid (10% vol/vol) and dialysate effluent (90% vol/vol). The mesothelial cells exposed to dialysis fluids under such conditions became activated cells compared with exposed to dialysate effluent (control) alone. Thus, synthesis by mesothelial cells of all tested substances was enhanced during exposure of the mesothelium to the dialysis fluids: interleukin-6: Dianeal 1.36, +257%; Dianeal 3.86, +181% (both P < 0.05); hyaluronic acid: Dianeal 1.36, +72%; Dianeal 3.86, +63% (both P < 0.05); tissue plasminogen activator: Dianeal 3.86, +33% (P < 0.05); and plasminogen activator/inhibitor-1: Dianeal 1.36, +28%; Dianeal 3.86, +38% (both P < 0.05). Our results show that the peritoneal mesothelium becomes activated when it is exposed to acidic, hyperosmotic dialysis fluids diluted with the dialysate effluent, in a manner that imitates the in vivo changes in these solutions during their intraperitoneal dwell.
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PMID:In vitro simulation of the effect of peritoneal dialysis solution on mesothelial cells. 904 Dec 17

The plasminogen activator (PA)-plasmin proteolytic system has recently received considerable attention because of its participation in a wide variety of biological activities and in pathological conditions involving tissue destruction. We examined the effects of interleukin-6 (IL-6) on PA activity and the gene expressions of tissue type (t) PA and PA inhibitor-1 (PAI-1) in human dental pulp (HDP) cells. IL-6 treatment induced significantly high PA activity in the HDP cells in a time- and dose-dependent manner, compared with nontreated controls. Western-blot analysis showed that tPA protein in the conditioned medium was stimulated by IL-6, compared with the control. The tPA and PAI-1 mRNA levels were increased in HDP cells treated with IL-6, as shown by reverse transcriptase-polymerase chain reaction. These results suggest that IL-6 stimulated PA activity through an enhancement of tPA gene expression and may be involved in extracellular matrix degradation through the stimulation of the PA-plasmin system of HDP cells.
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PMID:Stimulatory effect of interleukin-6 on plasminogen activator activity from human dental pulp cells. 964 Nov 8

Sepsis is commonly associated with disturbances of the hemostatic balance. Most of the pathophysiological changes in sepsis are caused by endotoxin acting directly through endothelial injury or indirectly through release of cytokines with procoagulant effects. The relation between cytokines and hemostatic parameters was assessed in 32 patients with sepsis. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes (TAT), tissue type plasminogen activator (t-PA) functional and antigen, plasminogen activator inhibitor-1 (PAI-1), plasminalpha2-antiplasmin complexes (PAP), D-Dimer, thrombomodulin (TM) and von Willebrand factor (vWF) were measured in patients and in 30 healthy subjects. The levels of cytokines TNF-alpha and interleukin-6 (IL-6) also were determined. A significant increase of F1+2, TAT, PAI-1, PAP, and D-Dimer was observed in septic patients as compared with controls (p<0.0001), whereas t-PA activity was significantly reduced (p<0.01). The markers of endothelial cell activation TM, vWF, and t-PA antigen also were elevated significantly as compared with the control group (p<0.01). Finally, we found a marked increase of TNF-alpha and IL-6 (p<0.0001). Whereas the increase of cytokine levels could be partially responsible for the hemostatic activation, it did not correlate with markers of endothelial activation in patients with sepsis.
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PMID:Endothelial cell and hemostatic activation in relation to cytokines in patients with sepsis. 1023 Aug 94

Intra-arterial desmopressin caused dose and time dependent increases (p <0.001 for all) in forearm blood flow (all doses) and plasma tissue plasminogen activator (t-PA) concentrations (desmopressin > or = 70 ng/min). Although plasma t-PA concentrations rose in both forearms, there was a modest local release of t-PA in the infused forearm (14 ng/100 mL of tissue/min, p <0.05). At desmopressin doses > or = 300 ng/min, plasma von Willebrand factor (vWf) and Factor VIII:C concentrations rose in both forearms (p <0.001) and correlated with the rise in interleukin-6 concentrations (r = 0.92, p <0.001: r = 0.85, p = 0.002 respectively). Neither desmopressin nor substance P caused t-PA, vWf or Factor VIII:C release in the patients, although desmopressin increased plasma interleukin-6 concentrations as in healthy volunteers. We conclude that desmopressin releases t-PA, vWf and Factor VIII:C predominantly via systemic mechanisms, possibly mediated by cytokine release. Patients with type 3 vWD appear to have a generalised failure to release t-PA acutely despite a normal interleukin-6 response to desmopressin infusion.
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PMID:Local and systemic effects of intra-arterial desmopressin in healthy volunteers and patients with type 3 von Willebrand disease. Role of interleukin-6. 1095 89

Liver regeneration following 70% partial hepatectomy leads to rapid activation of genes in the remnant liver. Interleukin-6 deficient (IL-6 -/-) mice have impaired liver regeneration and abnormalities in immediate early gene expression. In this study, the gene expression program in the IL-6 +/+ and -/- livers at 2 hours posthepatectomy was examined with a cDNA array representing 588 highly regulated mouse genes. Thirty-six percent of the 103 immediate early genes were induced differently in IL-6 +/+ compared with IL-6 -/- livers, implying regulation by IL-6. IL-6 treatment of the IL-6 -/- mice in the absence of hepatectomy induced a much smaller set of genes in the liver, suggesting that IL-6 cooperates with other hepatectomy-induced factors to activate the large number of genes. Northern blot analyses were used to verify gene expression data obtained from the arrays. The expression of urokinase type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), critical components of the urokinase plasminogen activator (uPA) system, was lower and delayed in IL-6 -/- livers. Despite the fact that active uPAR/uPA complex is critical for hepatocyte growth factor (HGF) activation, no differences were detected between the IL-6 +/+ and -/- livers in HGF activation as measured by receptor phosphorylation. On the contrary, the mitogen-activated protein kinase (MAPK) pathway was activated in IL-6 +/+ livers early during regeneration but remarkably delayed in IL-6 -/- livers. Defective liver regeneration may be explained by the large number of gene activation pathways altered in IL-6 -/- livers and further supports the finding that IL-6 is necessary for normal liver regeneration.
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PMID:Global changes in interleukin-6-dependent gene expression patterns in mouse livers after partial hepatectomy. 1139 26

We evaluated the effects of surgical invasion and vascular injury on hemostatic abnormalities in seventeen ASA I-II patients undergoing prolonged surgeries of eight hours or more consisting of tumor excision, radical neck dissection and free flap reconstruction in the maxillofacial region. As molecular markers of blood coagulation and surgical invasion, prothrombin fragment 1 + 2 (F 1 + 2), interleukin-6 (IL-6), tissue-type plasminogen activator (tPA), thrombomodulin (TM) and plasmin alpha 2-plasmin inhibitor complex (PIC) were measured during surgery and on the first and second postoperative days. The F 1 + 2 values increased significantly during surgery and decreased postoperatively, and reached the maximum at the end of surgery. Changes in IL-6 and tPA were similar to those of F 1 + 2, and there was a correlation in the levels of F 1 + 2 and IL-6 (r = 0.54), tPA (0.41) and PIC (0.30) at each measurement time. PIC and TM, however, did not show statistically significant changes intra- and postoperatively, nor was there any correlation between F 1 + 2 and TM values. From these results, we conclude that inflammatory mediators and endothelial stimulation activated by surgical invasion may influence hypercoagulability. Vascular injury, however, did not act as the main coagulation factor during prolonged maxillofacial surgery.
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PMID:[Effects of vascular injuries on hemostatic abnormalities in prolonged surgeries of maxillofacial malignant cancer]. 1199 46

Oncostatin M (OSM) is a glycoprotein cytokine that is produced by activated T-lymphocytes, monocytes, and macrophages. In a DNA synthesis assay, OSM reduced tritiated thymidine incorporation by 53% in Calu-1 lung carcinoma cells. Radiolabeled cDNAs from untreated Calu-1 cells and 30-h OSM-treated cells were used to probe duplicate nylon membrane cDNA expression arrays. This study revealed OSM-mediated expression of mRNAs encoding tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). Northern blot analysis showed that the steady-state level of tPA mRNA is nearly undetectable in Calu-1 cells. Exposure of these cells to OSM for 30 h increased tPA mRNA expression by 20-fold and PAI-1 mRNA expression by 5-fold. Exposure of these cells to other gp130 receptor family cytokines, including leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and IL-11, do not significantly affect DNA synthesis or induction of tPA/PAI-1. Western blot studies demonstrated that OSM mediates a marked increase in secretion of the tPA protein. Secreted tPA was present in the conditioned medium almost exclusively as tPA/PAI-1 complexes. Inhibitor studies demonstrated that OSM-mediated induction of tPA and PAI-1 mRNAs is largely dependent upon activation of the MEK1/2 pathway. The JAK3/STAT3 pathway potentially serves a secondary role in these regulatory events.
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PMID:Oncostatin M induces tissue-type plasminogen activator and plasminogen activator inhibitor-1 in Calu-1 lung carcinoma cells. 1209 Jul 57

Abnormalities in coagulation and haemostasis represent a well-known link between obesity and thrombosis (both arterial and venous). Several studies have shown that obese patients have higher plasma concentrations of all pro-thrombotic factors (fibrinogen, vonWillebrand factor (vWF), and factor VII), as compared to non-obese controls, with a positive association with central fat. Similarly, plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be higher in obese patients as compared to non-obese controls and to be directly correlated with visceral fat. Furthermore, obesity is characterized by higher plasma concentrations of anti-thrombotic factors, such as tissue-type plasminogen activator (t-PA) and protein C, as compared to non-obese controls, the increase in these factors being likely to represent a protective response partly counteracting the increase in pro-thrombotic factors. The issue of whether adipose tissue contributes directly to plasma PAI-1, its products stimulating other cells to produce PAI-1, or whether it primarily contributes indirectly has not yet been resolved. It has been proposed that the secretion of interleukin-6 (IL-6) by adipose tissue, combined with the actions of adipose tissue-expressed TNF-alpha in obesity, could underlie the association of insulin resistance with endothelial dysfunction, coagulopathy, and coronary heart disease. The role of leptin in impairing haemostasis and promoting thrombosis has been recently reported. Finally, some hormonal abnormalities (androgen, F, catecholamines) associated with the accumulation of body fat may contribute to the impairment of coagulative pathway in obesity. As to intervention strategies, dietary (i.e., low-fat high-fiber diet) and lifestyle (i.e., physical activity) measures have been demonstrated to be effective in improving the obesity-associated pro-thrombotic risk profile.
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PMID:Coagulation and fibrinolysis abnormalities in obesity. 1250 53

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6), viral load, CD4 T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-alpha (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.
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PMID:Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients. 1254 23


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