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)

To determine if host factors influence the time course and extent of lung injury after acute inhalation of ozone (O3), we evaluated the physiologic and biologic response of nine genetically diverse inbred strains of mice (C57BL/6J, 129/SvIm, BTBR, BALB/cJ, DBA/2J, A/J, FVB/NJ, CAST/Ei, and C3H/HeJ) exposed to O3 (2.0 ppm x 3 h). Whole lung lavage determined that 129/Svlm, BTBR, DBA/2J, and FVB/NJ had a peak increase in polymorphonuclear cells (PMNs) at 6 h, whereas C57BL/6J and CAST/Ei had a peak increase at 24 h after exposure; airway PMNs were minimally elevated in A/J and C3H/HeJ; BALB/cJ had a predominant lymphocytic influx. Interleukin-6 concentration in the lavage fluid was associated with the influx of PMNs, whereas the total protein in the lavage fluid did not always correlate with lavage cellularity. Respiratory responses were monitored using whole body plethysmography and enhanced pause index. C57BL/6J, BALB/cJ, 129/SvIm, and BTBR were highly sensitive to O3 and exhibited significant increases in enhanced pause to methacholine aerosol stimulation at 6 and 24 h after exposure to O3. In contrast, DBA/2J, A/J, FVB/NJ, CAST/Ei, and C3H/HeJ strains had demonstrated increases in sensitivity to MCh at 6 h after exposure, but responses had returned to near baseline by 24 h after exposure to O3. Epithelial cell proliferation as assessed by proliferating cell nuclear antigen staining was evident at 24 h after exposure to O3. C57BL/6J and A/J showed 4% proliferating cell nuclear antigen-positive cells; 129/SvIm, DBA/2J, and FVB/NJ had 1-3%; and BTBR, BALB/cJ, CAST/Ei, and C3H/HeJ had < 1%. Phenotypic measurements in six inbred strains were used for an in silico genome analysis based on the Roche mouse database. Consistent loci on chromosomes 1, 7, and 15 were among those identified to have a significant association with the phenotypes studied. In aggregate, our approach has identified O3-resistant (C3H/HeJ and A/J) and -vulnerable (C57BL/6J and 129/SvIm) strains of mice, and determined novel genomic loci, suggesting a clear genetic basis for the lung response to inhaled O3.
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PMID:Ozone-induced acute pulmonary injury in inbred mouse strains. 1497 36

The expression of proliferating cell nuclear antigen (PCNA) was studied in plasma cells in bone marrow biopsies from patients with multiple myeloma (MM) using a double immunostaining method. In the same samples, microvessel density (MVD), after staining with anti-CD34 antibodies, was determined before and after chemotherapy. The correlation of PCNA expression and MVD with other myeloma parameters (clinical stage, bone marrow plasma cell infiltration and serum interleukin-6 (IL-6)) was also investigated. The study population included 51 newly diagnosed MM patients, 15 patients in plateau phase after treatment and 15 normal controls. Pretreatment mean +/- SE values of PCNA, MVD, plasma cell infiltration and serum IL-6 were significantly higher than post treatment values and controls. Pretreatment PCNA expression correlated significantly with bone marrow MVD (p<0.05) plasma cell infiltration (p<0.01) and IL-6 (p<0.01). These findings show that the proliferative activity of plasma cells is related to the angiogenic activity in the bone marrow of multiple myeloma patients. Both PCNA and MVD correlate with markers of disease activity thus may provide additional information when included in the initial evaluation of myeloma bone marrow biopsies.
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PMID:Expression of proliferating cell nuclear antigen (PCNA) in multiple myeloma: its relationship to bone marrow microvessel density and other factors of disease activity. 1500 Aug 66

The shortage of available organs for liver transplantation has motivated the development of new surgical techniques such as reduced-size liver transplantation. Ischemia-reperfusion (I/R) associated with liver transplantation impairs liver regeneration. Ischemic preconditioning is effective against I/R injury in clinical practice of liver tumour resections. The present study evaluated the effect of ischemic preconditioning on reduced-size liver for transplantation and attempted to identify the underlying protective mechanisms. Hepatic injury and regeneration (transaminases, proliferating cell nuclear antigen [PCNA] labeling index, and hepatocyte growth factor [HGF]) were assessed after reduced-size orthotopic liver transplantation (ROLT). Energy metabolism, oxidative stress, tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) were examined as possible mechanisms involved in liver regeneration. Ischemic preconditioning reduced transaminase levels and increased HGF levels and the percentage of PCNA-positive hepatocytes after ROLT. This was associated with a decrease in oxidative stress following ROLT, whereas energy metabolism and hepatic IL-6 and TNF release were unchanged. The benefits of ischemic preconditioning on hepatic injury and liver regeneration could be mediated, at least partially by nitric oxide. These results suggest a new potential application of ischemic preconditioning in reduced-size liver transplantation.
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PMID:Protection of reduced-size liver for transplantation. 1530 28

Restenosis occurs in approximately one-third of patients with coronary or peripheral vascular disease who undergo balloon angioplasty or a surgical bypass procedure primarily because of the development of pseudointimal hyperplasia (PIH). Corticosteroids were effective in suppressing PIH in several experimental studies, but no clinical studies have been reported. To resolve this discrepancy, we studied the effects of preinjury administration of several doses of methylprednisolone (MP) at targeted times in a rat model of balloon aortic injury. Rats were given either no treatment or an intravenous injection of MP (0.5, 5.0, 50, or 500 mg/kg) 2 hours before aortic injury. Four hours later interleukin-6 (IL-6), IL-10, and macrophage migration inhibitory factor (MIF) concentrations in serum and tissue of injured aortas were assessed. Two weeks after injury, damaged aortas were harvested and studied histopathologically. Compared with results in controls, MP at a dose of 5 mg/kg significantly inhibited increases in plasma and tissue levels of IL-6 and significantly reduced the pseudointimal area, pseudointimal/medial area ratio, and proliferating cell nuclear antigen index in injured vessels. Administration of MP had no significant effect on the IL-10 or MIF level. Thus in a rat model of balloon aortic injury, preinjury administration of MP 5 mg/kg mitigated the development of PIH and cell proliferation and suppressed the postinjury increase in serum and tissue IL-6 concentrations. These results suggest that there is an appropriate dosage as well as appropriate timing for MP administration to suppress PIH.
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PMID:Effects of preinjury administration of corticosteroids on pseudointimal hyperplasia and cytokine response in a rat model of balloon aortic injury. 1559 66

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.
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PMID:Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats. 1695 81

The present study aims to investigate the possible effects of carvacrol obtained from origanum oil upon the regenerative feature of the liver subsequent to partial hepatectomy in rats. Male Wistar Albino rats, weighing 230+/-30g, were divided into three experiment groups. Group I (n=8) were used as sham operation group. Group II (n=8) were applied saline solution and hepatectomy. Carvacrol and hepatectomy (73mg/kg) were applied to Group III (n=8). One dose of test material was injected 1h before 68% partial hepatectomy. At the end of the experiments, blood and organs were removed. The liver regeneration rate of the rats was calculated measuring the weights of their liver before and after the hepatectomy. Hematoxylin and eosin, interleukin-6 (IL-6) and proliferating cell nuclear antigen (PCNA) treatments were applied to liver sections. Aspartate transaminase (AST), alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha) and IL-6 levels were determined in serum samples. The liver regeneration, mitotic index and PCNA index increased significantly in rats of Group III over the Group II at the 72nd hour after partial hepatectomy. Histological evaluations were also similar with these results of PCNA and mitotic indexes. In AST, ALT, TNF-alpha and IL-6 levels, there was no statistically significant difference. According to these results, it is concluded that carvacrol increases the liver regeneration rate.
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PMID:Effects of carvacrol upon the liver of rats undergoing partial hepatectomy. 1768 59

Phosphodiesterase type 4 (PDE4) is involved in the hydrolysis of cAMP in pulmonary vascular smooth muscle (PA-SMC) and immune inflammatory cells. Given that intracellular cAMP accumulation inhibits contraction and growth of PA-SMCs as well as inflammatory cell functions, we investigated the effects of the PDE4 inhibitor 3-cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide (roflumilast), on pulmonary hypertension (PH) in rats. Treatment with roflumilast (0.5 or 1.5 mg x kg(-1) day(-1)) from day 1 to day 21 after monocrotaline (MCT) injection (60 mg x kg(-1) s.c.) attenuated PH development: pulmonary artery pressure, right ventricular hypertrophy, and muscularization of distal vessels on day 21 were decreased compared to control MCT-treated rats. Roflumilast (1.5 mg x kg(-1) day(-1)) also reduced the increases in interleukin-6 and monocyte chemotactic protein-1 mRNAs observed in lung tissue on day 21 without affecting the rise in interleukin-1beta mRNA on days 1 and 21. Roflumilast (1.5 mg x kg(-1) day(-1)) from day 21 to day 42 after MCT reversed established PH, almost normalizing pulmonary artery pressure and structure, and suppressing proliferating cell nuclear antigen-positive cells in pulmonary vascular walls. Treatment with roflumilast similarly attenuated PH development due to chronic hypoxia. Treatment of human PA-SMCs with roflumilast N-oxide, the active metabolite of roflumilast, at concentrations up to 10(-6) M, potentiated PA-SMC growth inhibition induced by prostacyclin (10(-6) M) or interleukin-1beta (10 ng x ml(-1)) but was inactive on its own. In conclusion, the PDE4 inhibitor roflumilast significantly attenuates pulmonary vascular remodeling and hypertension induced by chronic hypoxia or MCT and reverses established PH after MCT administration.
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PMID:Effects of roflumilast, a phosphodiesterase-4 inhibitor, on hypoxia- and monocrotaline-induced pulmonary hypertension in rats. 1938 93

Inflammation induced by chronic exposure to ultraviolet (UV) radiation has been implicated in various skin diseases. We formulated the hypothesis that a high-fat diet may influence the UV-induced inflammatory responses in the skin. C57BL/6 mice were fed a high-fat diet or control diet and exposed to UVB radiation (120 mJ/cm(2)) three times/week for 10 weeks. The mice were then sacrificed and skin and plasma samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. We found that the levels of inflammatory biomarkers were increased in the UVB-exposed skin of the mice fed the high-fat diet than the UVB-exposed skin of the mice fed the control diet. The levels of inflammatory biomarkers of early responses to UVB exposure (e.g., myeloperoxidase, cyclooxygenase-2, prostaglandin-E(2)), proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser(473)) were higher in high-fat-diet-fed mouse skin than control-diet-fed mouse skin. The plasma levels of insulin growth factor-1 were greater in the UVB-irradiated mice fed the high-fat diet than the UVB-irradiated mice fed the control diet, whereas the levels of plasma adiponectin were significantly lower. This pronounced exacerbation of the UVB-induced inflammatory responses in the skin of mice fed a high-fat diet suggests that high-fat diet may increase susceptibility to inflammation-associated skin diseases, including the risk of skin cancer.
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PMID:High-fat diet exacerbates inflammation and cell survival signals in the skin of ultraviolet B-irradiated C57BL/6 mice. 1974

Circulating endothelial progenitor cells (CEPCs) play an important role in the process of atherosclerosis. Most previous studies on CEPC in systemic lupus erythematosus (SLE) patients were on their number and some functions and the results were not consistent. No studies on their anti-inflammatory function and integrated status were reported. The purpose of this study was to determine the number, function (including anti-inflammatory function), and the integrated status of CEPCs in active SLE patients. The study was performed in 35 active SLE patients (28 females, 7 males) and 35 age-and gender-matched healthy controls. CEPC number was determined by Fluorescence-Activated Cell Sorting. Proliferation capacity of CEPC was assessed by PCNA staining. Adhesion capacity of CEPC to fibronectin and adhesion capacity of THP1 cell to CEPC were determined by cell adhesion assay. Migratory capacity of CEPC was measured by transwell chamber assay and the potential to form tubes on Matrigel of CEPC was determined by in vivo tube formation on Matrigel test. The expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) assessed by quantitative PCR as well as the expression of intercellular adhesion molecule-1 (ICAM-1) and phosphorylated-Akt (p-Akt) assessed by western-blotting were used to evaluate the anti-inflammatory function and cell status of CEPCs. The number of CEPC in SLE patients was not different from that in control (p > 0.05). Proliferation capacity of CEPC was decreased in active SLE patients (p = 0.027). Adhesion capacity of CEPC to fibronectin was decreased (p = 0.04) in SLE patients and adhesion capacity of THP1 cell to CEPC was increased in SLE patients (p < 0.001). Migratory activity was reduced in patient CEPCs (p < 0.001). Capacity of CEPCs to form tube on Matrigel was decreased in SLE patients (p < 0.001). Expression of iNOS and IL-6 (p < 0.001, p = 0.006, respectively) and ICAM-1 were increased in CEPC of SLE patients and expression of p-Akt was decreased in CEPC of SLE patients. Our data show that CEPC number in active SLE patients was not significantly different from healthy controls, but their functions were partly impaired, including proliferation, adhesion, migration, and tube formation. Bad cell status and increased susceptibility to inflammatory process of CEPCs in active SLE were also observed in our study.
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PMID:Comparative study on circulating endothelial progenitor cells in systemic lupus erythematosus patients at active stage. 1984 36

TNFAIP1 is a protein which can be induced by tumor necrosis factoralpha (TNFalpha) and interleukin-6 (IL-6), it may play roles in DNA synthesis, DNA repair, cell apoptosis and human diseases. However, very little has been known about how TNFAIP1 acts in these physiological processes. In this paper, CK2beta was identified as a partner of TNFAIP1 by screening the HeLa cDNA library in yeast two-hybrid system with TNFAIP1 as a bait. Furthermore, it was demonstrated that CK2 could phosphorylate TNFAIP1 in vitro and in vivo, which facilitated the distribution of TNFAIP1 in nucleus and enhanced its interaction with PCNA. It is suggested that the phosphorylation of TNFAIP1 may be required for its functions.
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PMID:CK2 phosphorylates TNFAIP1 to affect its subcellular localization and interaction with PCNA. 1985 86


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