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

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, causes equine leukoencephalomalacia, a condition not reproduced in any other species. We hypothesized that direct exposure of murine brain to FB1 will result in neurotoxicity, characterized by biochemical and pathological alterations. The present study compared the toxicity of FB1 in mouse brain after an intracerebroventricular (icv) or subcutaneous (sc) infusion. Female BALB/c mice (5/group) were infused (0.5 microl/h) with total doses of 0, 10 or 100 microg FB1 in saline over 7 days via osmotic pumps implanted either via icv cannulation of the ventricle or via the sc route. One day after the last day of treatment, brains were dissected either fresh or after intracardiac paraformaldehyde fixation. In mice given 100 microg of FB1 icv, FluoroJade B staining revealed neurodegeneration in the cortex, and anti-glial fibrillary acidic protein staining detected activated astrocytes in the hippocampus. High performance liquid chromatography indicated accumulation of free sphinganine in animals given FB1 icv in all brain regions and increased free sphingosine after the 100 microg FB1 in the cortex. The concentration of cortical sphingomyelin and complex sphingolipids remained unchanged. The icv administration of FB1 induced expression of tumor necrosis factor alpha, interleukin-1beta, interleukin-6 and interferon gamma after both doses, assayed by the real-time polymerase chain reaction. The sc administration of 100 microg FB1 caused slight sphinganine accumulation and increased IL-1beta expression in cortex only. Results indicated that icv injection of FB1 caused neurodegeneration with simultaneous inhibition of de novo ceramide synthesis, stimulation of astrocytes, and upregulation of pro-inflammatory cytokines in the murine brain. A relative lack of FB1 availability into the brain could be responsible for the absence of its neurotoxicity in mouse.
 ...
PMID:Fumonisin B1-induced neurodegeneration in mice after intracerebroventricular infusion is concurrent with disruption of sphingolipid metabolism and activation of proinflammatory signaling. 1571 42

Dengue virus infection can cause mild dengue fever (DF) or severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Cytokines are believed to be involved in the pathogenesis of dengue infection. However, the role of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in dengue infection is unclear. In this study, serum levels of MIF in adult dengue patients with different disease severity and clinical outcome were determined and compared with the levels of other cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, and interferon gamma (IFN-gamma), in the same patients. Serum levels of MIF, IL-6, and IL-10, but not IFN-gamma or TNF-alpha, were higher in all DHF patients who died than in DHF survivors and DF patients. We conclude that in addition to IL-6 and IL-10, elevated levels of serum MIF are a potential predictor of disease severity and clinical outcome in dengue patients.
 ...
PMID:Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. 1640 59

The physiological effects of the flavone, apigenin on bone cells were studied. We first show that apigenin inhibits tumor necrosis factor alpha (TNFalpha)- and interferon gamma (IFNgamma)-induced secretion of several osteoclastogenic cytokines from MC3T3-E1 mouse calvarial osteoblast cell line. Ligands of the TNF receptor family constitute the most potent osteoclastic cytokines. In MC3T3-E1 cells, apigenin dose-dependently (from 5 to 20 microM) inhibits TNFalpha-induced production of the osteoclastogenic cytokines, IL-6 (interleukin-6), RANTES (regulated upon activation, normal T cell-expressed and -secreted), monocyte chemoattractant protein-1 (MCP-1) and MCP-3. In addition, apigenin inhibits IFNgamma-stimulated secretion of monokines, CXCL-9, and -10 in MC3T3-E1 cells. Next, we show that apigenin strongly inhibits differentiation of 3T3-L1 preadipocytes to adipocytes with attendant inhibition of adipocyte differentiation-induced IL-6, MCP-1, and leptin production. Inhibition of adipogenic differentiation by apigenin could be due to induction of osteogensis as it robustly upregulates mRNA levels of bone morphogenetic protein-6 (BMP-6). Finally, the presence of apigenin inhibited osteoclast differentiation from the RAW 264.7 cell line by reducing receptor activator of nuclear factor kappa ligand (RANKL)-induced expression of tartrate-resistant acid phosphatase (TRAP), RANK, and calcitonin receptor but not CCR1, resulting in the inhibition of multinucleated osteoclast formation. Similarly, apigenin inhibited expression of the osteoclast differentiation markers TRAP, RANK, and c-Fms in osteoclast precursor cells obtained from mouse bone marrow following treatment with RANKL and macrophage colony stimulating factor (MCSF). Furthermore, apigenin induced apoptosis of mature osteoclasts obtained from rabbit long bone and inhibited bone resorption. In all instances, a structurally related compound, flavone had no significant effect. These data suggest that apigenin has multiple effects on all three bone cells that could prevent bone loss in vivo.
 ...
PMID:Attenuation of osteoclastogenesis and osteoclast function by apigenin. 1675 Jan 76

The exact pathological background of inflammatory bowel disease has not been clarified yet. Many aspects of genetical and environmental factors, as well as certain alterations of the functions of epithelial cells and immunoregulation which may attenuate chronic inflammation in the gastrointestinal tract are known. These three components have many connecting points. Among the inflammatory bowel disease genes we know only the function of the NOD2/CARD gene, and we have some idea about the OCTN and DRG genes. The function of the intestinal epithelial cells is changed in inflammatory bowel disease. The latter two genes may have a role in the increased permeability, so as the tumor necrosis factor alpha, interferon gamma may play affect it. The interleukin-10 helps the mucosal integrity. The interleukin-6 production is elevated in these diseases, and the interleukin-8 level can be elevated in case of mutation of toll like receptor 5. The tumor necrosis factor alpha, interferon gamma and lymphotoxin-3-alpha increased the chemokine secretion and adhesion molecule expression also. The amount of certain cytokines are changed in inflammatory bowel disease. There were no association between the incidence and phenotype of Crohn's disease and cytokine gene polymorphisms, except the interleukin 6 gene. It seems that these alterations are secondary, and don't play a major role in the pathogenesis of inflammatory bowel disease.
 ...
PMID:[Molecular biology background of inflammatory bowel disease]. 1697 77

Peroxisome proliferator-activated receptors (PPARs) beta/delta and gamma have overlapping roles in the negative regulation of inflammatory response genes. Ligand activation of PPARgamma protects against experimental colitis in mice. PPARbeta/delta can negatively regulate inflammation and is highly expressed in the epithelial cells of the colon, therefore PPARbeta/delta may also have a role in experimental colitis. In these studies, colitis was induced by dextran sodium sulfate (DSS) treatment in wild-type and PPARbeta/delta-null mice, with and without the PPARbeta/delta specific ligand GW0742. PPARbeta/delta-null mice exhibited increased sensitivity to DSS-induced colitis, as shown by marked differences in body weight loss, colon length, colonic morphology, myeloperoxidase activity and increased expression of mRNAs encoding the inflammatory markers interferon gamma, tumor necrosis factor-alpha, and interleukin-6 compared to similarly treated wild-type mice. Interestingly, these differences were not affected by ligand activation of PPARbeta/delta in either genotype. These studies demonstrate that PPARbeta/delta expression in the colonic epithelium inhibits inflammation and protects against DSS-induced colitis through a ligand-independent mechanism.
 ...
PMID:PPARbeta/delta protects against experimental colitis through a ligand-independent mechanism. 1740 49

Cytochromes P450 (P450s) are down-regulated in hepatocytes in response to inflammation and infection. This effect has been extensively studied in animal models, but significantly less is known about responses in humans and even less about responses in the absence of inducing agents. This article focuses on the effects of bacterial lipopolysaccaride (LPS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF), interferon gamma (IFN), transforming growth factor-beta (TGF) and interleukin-1 beta (IL-1) on expression of CYP2B6 and the CYP2C mRNAs in human hepatocytes. These effects were compared with responses of the better studied and more abundant CYP3A4. CYP3A4 and CYP2C8 were down-regulated by all cytokine treatments. CYP2C18, which is expressed at very low levels in liver, was unaffected by cytokine treatments. The other CYP2Cs and CYP2B6 showed cytokine-specific effects. CYP2C9 and CYP2C19 showed almost identical response patterns, being down-regulated by IL-6 and TGF but not significantly affected by LPS, TNF, IFN, or IL-1. CYP2B6 mRNA responded only to IL-6 and IFN. IL-6 down-regulated the mRNAs of all P450s studied. Western blot analysis of P450 protein expression supported the mRNA data to a large extent, although some inconsistencies were observed. Our results show that human CYP2C8, 2C9, 2C18, 2C19, 2B6, and 3A4 responses to inflammation are independently regulated and indicate that this fine control may have a critical effect on human drug responses in disease states.
 ...
PMID:Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. 1757 8

Our view of white adipose tissue (WAT) has changed over the last decade, from an inert triglyceride storage tissue to a highly active metabolic organ. Indeed, WAT secretes proinflammatory cytokines such TNF-a, interleukin-1 (IL-1), interleukin-1 receptor antagonist (IL-1Ra), and interleukin-6 (IL-6), and chemokines such as monocyte chemoattractant protein-1 (MCP-1), interferon gamma inducible protein 10 (IP-10), interleukin-8 (IL-8), RANTES, and peptides with hormone-like actions such as adiponectin, leptin and resistin. Through their paracrine actions these factors contribute to local WAT inflammation, neoangiogenesis and differentiation. On entering the systemic circulation they can contribute to creating or maintaining a systemic inflammatory state, hypertension and insulin resistance, and can also affect central control of food intake. When located around organs such as the kidney, heart and blood vessels, WAT can adversely affect organ function by secreting cytokines and chemokines. For example, perivascular WAT which secretes proatherogenic cytokines and chemokines and which is present around large and medium-sized arteries, could contribute to the development of atherosclerotic lesions by attracting inflammatory cells and stimulating neoangiogenesis, thereby amplifying the chronic vascular inflammation which is the hallmark of atherosclerosis.
 ...
PMID:[White adipose tissue, inflammation and atherosclerosis]. 1822 44

The secretion of tumour necrosis factor-alpha (TNFalpha), interleukin-1alpha (IL-alpha) and interleukin-6 (IL-6) by a human astrocytoma cell fine was studied 1 h, 3 h, 6 h and 24 h after infection with tachyzoites from three Toxoplasma gondii strains (virulent, RH; cystogentc, 76K and Prugniaud strains). The astrocytoma cell fine constitutively secreted TNFalpha and IL-6, but no IL-1alpha. A positive control was obtained by stimulation with phorbol esters inducing a significant increase (p < 0.05) in TNFalpha and IL- 6 secretion but not in IL-1alpha, while lipopolysaccharide (alone and after priming), interferon gamma, ionophore A 23187 and sera positive to T. gondii did not induce any increase in cytokine levels. None of the tachyzoites, whatever their virulence, induced a significant increase in cytokine production at any time in the study. Tachyzoites did not inhibit the secretion induced by phorbol esters.
 ...
PMID:Infection with Toxoplasma gondii does not Alter TNFalpha and IL-6 Secretion by A human Astrocytoma Cell Line. 1847 55

This study compared the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interferon gamma (IFN-gamma) in 78 Colombian patients, from two ethnic groups, with dengue virus infection. TNF-alpha levels were significantly higher in Afro-Colombians than in Mestizos and IL-6 levels were significantly higher in Mestizos than in Afro-Colombians, during the acute phase. IFN-gamma levels were similar in both ethnic groups. Significantly higher TNF-alpha levels were found in Afro-Colombians than in Mestizos in both dengue fever (DF) and dengue hemorrhagic fever (DHF). The IL-6 levels were higher in Mestizos than in Afro-Colombians among patients with DF, but levels of this cytokine were higher in Afro-Colombians than in Mestizos among patients with DHF. Levels of IFN-gamma were higher in patients with DHF than DF. Higher levels of these cytokines were observed in secondary infection. These results suggest that ethnicity may contribute to differences in immune responses to dengue infections.
 ...
PMID:Serum levels of cytokines in two ethnic groups with dengue virus infection. 1898 2

We present a 7-year-old boy diagnosed as having salmonella encephalopathy. He developed severe consciousness disturbance following enterocolitis. Electroencephalography showed diffuse and high-voltage slow activity but MR images of the brain were normal. Examination of inflammatory cytokines in serum and cerebrospinal fluid revealed high levels of interleukin-6, -8, and -10, and interferon gamma. Salmonella typhimurium was detected in a stool specimen. He was diagnosed as having salmonella-associated encephalopathy that had features of septic encephalopathy and quickly responded to high-dose methylpredonisolone therapy. High-dose methylpredonisolone was considered to be an effective treatment for hypercytokine-mediated S. encephalopathy.
 ...
PMID:Salmonella encephalopathy successfully treated with high-dose methylpredonisolone therapy. 1921 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>