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)

We describe the characterization of a spontaneously transformed chicken monocytic cell line that developed as a single colony of cells in a heterophil culture that was inadvertently left in the incubator over a period of 25 days. These cells, hitherto named HTC, grow efficiently at both 37 or 41 degrees C in culture medium containing either 5% FBS or 2% chicken serum. The HTC cells are acid phosphatase positive, show expressions of both class I and class II major histocompatibility complex (MHC), CD44, K1, and K55 cell surface antigens, and engulf latex beads, produce nitrite and interleukin-6 on stimulation with bacterial lipopolysaccharide (LPS). Treatment with phorbol myristate acetate (PMA) induces respiratory burst in HTC cells and the secretion of matrix metalloproteinase (MMP) into culture medium. Using gene-specific primers and reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of mRNA trancripts for interferon-gamma (IFN-gamma), interleukin-1 (IL-1), interleukin-6 (IL-6), nitric oxide synthase (NOS), matrix metalloproteinase-2 (MMP-2), and transforming growth factor-beta (TGF-beta) were detected. Lipopolysaccharide (LPS) treatment of HTC cells modulated IL-1, IL-6, IFN-gamma, NOS mRNA levels as detected by RT-PCR analyses. Using different avian tumor virus gene-specific primers and PCR, the HTC cells were positive for the presence of avian leukosis virus (ALV) and Marek's disease virus (MDV) but negative for reticuloendothelial virus (REV), chicken infectious anemia virus (CIAV), and herpes virus of turkeys (HVT). The production of ALV antigens by HTC cells was further confirmed using p27 gag protein ELISA. Collectively, these results show that the HTC cells belong to myeloid/macrophage lineage and were likely transformed by ALV and MDV but retain many interesting and useful biological activities.
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PMID:Characterization of a spontaneously transformed chicken mononuclear cell line. 1452 38

Chronic hypoxia is implicated in lung fibrosis, which is characterized by enhanced deposition of extracellular matrix (ECM) molecules. Transforming growth factor-beta (TGF-beta) plays a key role in fibroblast homeostasis and is involved in disease states characterized by excessive fibrosis, such as pulmonary fibrosis. In this study, we investigated if hypoxia modulates the effects of TGF-beta on the expression of gelatinases: matrix metalloproteinase (MMP)-2 and MMP-9, interstitial collagenases: MMP-1 and MMP-13, tissue inhibitors of MMP (TIMP), collagen type I and interleukin-6 (IL-6). Primary human lung fibroblasts, established from tissue biopsies, were cultivated under normoxia or hypoxia in the presence of TGF-beta1, TGF-beta2 or TGF-beta3. Gelatinases were assessed by gelatin zymography and collagenases, TIMP, collagen type I and IL-6 by ELISA. Under normoxia fibroblasts secreted MMP-2, collagenases, TIMP, collagen type I and IL-6. TGF-betas significantly decreased MMP-1 and increased TIMP-1, IL-6 and collagen type I. Hypoxia significantly enhanced MMP-2, and collagenases. Compared to normoxia, the combination of TGF-beta and hypoxia reduced MMP-1, and further amplified the level of TIMP, IL-6, and collagen type I. Thus, in human lung fibroblasts hypoxia significantly increases the TGF-betas-induced secretion of collagen type I and may be associated to the accumulation of ECM observed in lung fibrosis.
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PMID:Hypoxia modulates the effects of transforming growth factor-beta isoforms on matrix-formation by primary human lung fibroblasts. 1456 88

Beta2-adrenoceptor agonists are widely used in the treatment of pulmonary diseases. We have investigated the relaxant and anti-inflammatory activities of NCX-950 (alpha'-[[(1,1-dimethylethy)amino]methyl]-4-hydroxy-1,3-benzenedimethanol nitrate) (a nitric oxide-releasing salbutamol) in human isolated bronchi and on lipopolysaccharide (LPS)-induced acute airway inflammation in mice. NCX-950 (10(-8)-10(-5) M) elicited a relaxation of human isolated bronchi moderately higher than salbutamol, which was reduced by a beta-adrenergic blocking drug, propranolol, but not by an inhibitor of guanylate cyclase, ODQ (1H-[1,2,4]oxadiazolo[4,3-] quinolaxin-1-one). The treatment of mice with NCX-950 (1, 10, and 100 microM aerosol) markedly inhibited the neutrophil influx induced by LPS aerosol in bronchoalveolar lavage (BAL) fluid, whereas salbutamol at equimolar doses elicited a moderate inhibition. Pretreatment of mice with NCX-950 (100 microM) also significantly reduced tumor necrosis factor-alpha, interleukin-6 (IL-6), transforming growth factor-beta, and matrix metalloproteinase-9 release in BAL fluid, whereas salbutamol was ineffective. Propranolol, but not ODQ, suppressed the inhibitory activity of NCX-950 on neutrophil influx and IL-6 release in BAL fluids. A nitric oxide-releasing sildenafil NCX-911 [(5-[2-ethoxy-5-(4-methylpiperidinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one nitrate)], but not sildenafil (100 microM) also reduced the neutrophil influx following LPS exposure in mice. This study reported that NCX-950 elicits potent relaxant and anti-inflammatory activities compared with salbutamol, and these effects may be mainly due to the activation of the beta2-adrenoceptor rather than the cGMP pathway.
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PMID:A nitric oxide-releasing salbutamol elicits potent relaxant and anti-inflammatory activities. 1508 49

Previous analyses of pleural effusions of different origin revealed high levels of matrix metalloproteinase-9 proenzyme (proMMP-9), predominantly in parainfectious exudates. To confirm the etiological association with inflammation and to explore time course of release of proMMP-9 under conditions of a local inflammatory reaction, the authors estimated proMMP-9 in pleural fluids of patients undergoing therapeutic talc pleurodesis (n = 20) and explorative thoracoscopy (n = 4), before, and at different time intervals after the intervention. The authors also compared proMMP-9 values with proinflammatory markers, such as interleukin-6 (IL-6), C-reactive protein (CRP), and leukocyte count. As revealed through scanning substrate electrophoresis, proMMP-9 levels increased within the first hours a!nd culminated 16 to 48 hours after intervention, amounting to 1.5- to 102 -fold of initial concentration (mean = 14.8 -fold). MMP-9 proenzyme values significantly correlated with the levels of proinflammatory cytokine IL-6 (r =.79, n = 47, p <.01) and with neutrophil counts (r =.75, n = 45, p <.01). In conclusion, the results present proMMP-9 as a novel early indicator of acute host-response in pleural space that complements traditional proinflammatory markers and might be useful in monitoring pleural inflammatory processes.
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PMID:Progelatinase B/matrix metalloproteinase-9 proenzyme as a marker of pleural inflammation. 1520 35

We performed an observational study on 137 patients undergoing carotid endarterectomy (CEA). Patients on statins were less likely to have had symptoms in the 4 weeks before CEA (p = 0.0049) and were less likely to have spontaneous cerebral embolization detected by transcranial Doppler (p = 0.0459). Carotid plaques retrieved at CEA from patients taking statins revealed significantly lower concentrations of matrix metalloproteinase-1 (p = 0.0176), matrix metalloproteinase-9 (p = 0.0018), and interleukin-6 (p = 0.0005).
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PMID:Comparison of levels of matrix metalloproteinases, tissue inhibitor of metalloproteinases, interleukins, and tissue necrosis factor in carotid endarterectomy specimens from patients on versus not on statins preoperatively. 1521 30

It has become clear that spinal cord glia (microglia and astrocytes) importantly contribute to the creation of exaggerated pain responses. One model used to study this is peri-spinal (intrathecal, i.t.) administration of gp120, an envelope protein of HIV-1 known to activate glia. Previous studies demonstrated that i.t. gp120 produces pain facilitation via the release of glial proinflammatory cytokines. The present series of studies tested whether spinal nitric oxide (NO) contributes to i.t. gp120-induced mechanical allodynia and, if so, what effect NO has on spinal proinflammatory cytokines. gp120 stimulation of acutely isolated lumbar dorsal spinal cords released NO as well as proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta (IL1), interleukin-6 (IL6)), thus identifying NO as a candidate mediator of gp120-induced behavioral effects. Behaviorally, identical effects were observed when gp120-induced mechanical allodynia was challenged by i.t. pre-treatment with either a broad-spectrum nitric oxide synthase (NOS) inhibitor (L-NAME) or 7-NINA, a selective inhibitor of NOS type-I (nNOS). Both abolished gp120-induced mechanical allodynia. While the literature pre-dominantly documents that proinflammatory cytokines stimulate the production of NO rather than the reverse, here we show that gp120-induced NO increases proinflammatory cytokine mRNA levels (RT-PCR) and both protein expression and protein release (serial ELISA). Furthermore, gp120 increases mRNA for IL1 converting enzyme and matrix metalloproteinase-9, enzymes responsible for activation and release of proinflammatory cytokines.
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PMID:HIV-1 gp120 stimulates proinflammatory cytokine-mediated pain facilitation via activation of nitric oxide synthase-I (nNOS). 1528 92

Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of infrared radiation on skin aging. In addition to photons, heat is likely to be generated as a consequence of infrared irradiation, and heat shock is widely considered to be an environmental stress. Here we investigated the effect of heat shock on the expressions of matrix metalloproteinase (MMP)-1, MMP-2, and MMP-3 in cultured human skin fibroblasts. Heat shock induced the expression of MMP-1 and MMP-3, but not MMP-2, at the mRNA and protein levels in a temperature-dependent manner, and caused the rapid activation of three distinct mitogen-activated protein kinases (MAPK), extracelluar signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. The heat shock-induced MMP-1 and MMP-3 expression was suppressed by the inhibition of ERK and JNK but not by p38 MAPK inhibition. Furthermore, heat shock increased the synthesis and release of interleukin-6 (IL-6) into culture media. The specific inhibition of IL-6 using a monoclonal antibody against IL-6 greatly reduced the expression of MMP-1 and MMP-3 induced by heat shock. Taken together, our results suggest that ERK and JNK play an important role in the induction of MMP-1 and MMP-3 by heat shock and that the heat shock-induced expression of MMP-1 and MMP-3 is mediated via an IL-6-dependent autocrine mechanism.
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PMID:Heat shock-induced matrix metalloproteinase (MMP)-1 and MMP-3 are mediated through ERK and JNK activation and via an autocrine interleukin-6 loop. 1561 May 7

Recent experimental data have shown that levels of matrix metalloproteinase-9 (MMP-9) increase after traumatic brain injury (TBI), degrading components of the basal lamina disrupting the blood-brain barrier. However, the post-traumatic secretion patterns of MMP-9 in humans are unknown. We measured the concentration of MMP-9 in plasma after TBI at the same time as the concentration of interleukin-6 (IL-6) in serum. Levels of MMP-9 and IL-6 in systemic arterial and jugular venous blood from seven patients with TBI were measured on days 0 and 1 post-injury. All patients underwent hypothermia at 32-35 degrees C as soon as possible after admission. Before induction of hypothermia, levels of MMP-9 in arterial and internal jugular venous blood exceeded the normal range. Higher MMP-9 levels were detected in internal jugular venous blood than in arterial blood. After hypothermia had been induced, MMP-9 levels in arterial blood and internal jugular venous blood decreased significantly, to within the normal range. In addition to these changes, a significant correlation was seen between levels of MMP-9 and IL-6 in internal jugular venous blood during the investigation period. These results indicate that MMP-9 is elevated in patients with acute TBI, and may play an important role in traumatic brain damage. The elevation of MMP-9 is associated with inflammatory events following TBI. Hypothermic intervention may suppress the elevation of MMP-9 with suppression of the inflammatory response, affording neuroprotection in TBI.
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PMID:Increased matrix metalloproteinase-9 in blood in association with activation of interleukin-6 after traumatic brain injury: influence of hypothermic therapy. 1568 62

The objectives of this work were to observe the multiple immuno-regulating effects of vasoactive intestinal peptide (VIP) on synovial cells of collagen induced arthritis (CIA) rats and to determine whether the transcriptional factor-kappaB (NF-kappaB) signal pathway was involved. CIA was induced using female Wistar rats by native bovine type II collagen (C II) emulsified with complete Freund's adjuvant (CFA). Synovial cells from the knees of the CIA rats were cultivated, and the effects of VIP and VIP receptor inhibitor ([D-P-Cl-Phe(6),Leu(17)]-VIP, I) on proliferation and apoptosis of the synovial cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carcoxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), flow cytometry, and DNA integrity. The effects of VIP and [D-P-Cl-Phe(6), Leu(17)]-VIP on mRNA expression of several cytokines in the synovial cells including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), regulated upon activation, normal T-cell expressed and secreted (RANTES), inducible NO synthase (iNOS), matrix metalloproteinase-2 (MMP-2) and MMP-9 were estimated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Effects of VIP and [D-P-Cl-Phe(6), Leu(17)]-VIP on NF-kappaB activity were analyzed using luciferase gene reporter assays. Effects of VIP and [D-P-Cl-Phe(6),Leu(17)]-VIP on p65NF-kappaB expression of the synovial cells were examined by Western blot. Seventy-five percent of the induced rats developed CIA. VIP has multiple effects on synovial cells of CIA rats including decreasing proliferation, inducing apoptosis, and down-regulating mRNA expression of several inflammatory factors. VIP was found to play immuno-regulating roles through the down-regulation of the activity and expression of NF-kappaB, whereas VIP receptor blockade was found to counteract all the effects. In conclusion, VIP was found to ameliorate synovial cell functions of CIA rats through binding with receptors and further down-regulating NF-kappaB signal pathway, suggesting VIP is a potential anti-inflammatory and anti-rheumatic agent of CIA by blocking NF-kappaB.
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PMID:Vasoactive intestinal peptide ameliorates synovial cell functions of collagen-induced arthritis rats by down-regulating NF-kappaB activity. 1592 Nov 57

Multiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption. Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78+/-91.27 vs. 59.25+/-33.09 ng/mL, p<0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p<0.001, p<0.03, p<0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p<0.0001, p<0.01, respectively). MMP-9 levels were lower in patients compared with controls (p<0.001), whereas IL-6 and bone resorption marker levels were higher in patients than in controls (p<0.001 in all cases). Significant correlation was found between infiltration, MMP-9, free urine pyd, free urine dpd and NTx for each stage of the disease (p<0.03, p<0.003, p<0.002, p<0.003 and p<0.001, respectively). Levels of MMP-9 and of IL-6 in multiple myeloma correlate well with bone turnover rate and may be useful in disease evaluation.
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PMID:Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease. 1659 48


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