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)

Under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee, primary hepatocyte cultures were prepared from second-trimester fetal liver specimens. We have shown for the first time that fetal hepatocytes have the capacity to produce an acute-phase response on treatment with inflammatory mediators. Addition of interleukin-6 to the cultures resulted in strong induction of C-reactive protein and alpha-1-antichymotrypsin expression, whereas albumin expression was repressed. In contrast to interleukin-6, transforming growth factor-beta did not induce C-reactive protein expression. However, as in adult hepatocytes, fetal cells responded to transforming growth factor-beta by reduced albumin synthesis. We were able to show by virtue of fluorescein excretion into sealed clefts that fetal hepatocytes have the functional capacity to form bile. Our findings indicate that second-trimester hepatocytes can be regarded as fairly mature liver cells.
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PMID:Human fetal hepatocytes respond to inflammatory mediators and excrete bile. 171 Oct 3

HepG2 cells were cultured for 7 days in serum-free medium in the presence of interleukin-6 (IL-6), retinoic acid (RA) or dexamethasone (DX), and some plasma proteins secreted to the media were determined by electroimmunoassay whereas the contents of specific mRNAs in the cells was evaluated by Northern blot hybridization. Interleukin-6 maximally stimulated synthesis of alpha-1-antichymotrypsin between days 1 and 3 whereas the response of fibrinogen was delayed to days 3 to 7. Retinoic acid increased the effect of IL-6 on alpha-1-antichymotrypsin (ACT) and fibrinogen (FBG) on the level of both proteins and mRNAs. Synthesis of albumin was slightly inhibited by IL-6 and RA, and synthesis of transferrin was increased by RA but not by IL-6. Dexamethasone had small enhancing effect on the action of IL-6. These results suggest that long-term HepG2 cultures may provide an experimental model for liver acute phase response during chronic inflammation.
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PMID:Long-term culture of HepG2 hepatoma cells as a model for liver acute phase response during chronic inflammation. Effects of interleukin-6, dexamethasone and retinoic acid. 769 40

Human hepatoma cells (HepG2) synthesize and secrete several plasma proteins that are inhibited in a time- and dose-dependent manner after vaccinia virus infection. However, infection of the HepG2 cells with a low dose of the virus (up to 1 plaque forming unit/cell) stimulated the expression of alpha-1-antichymotrypsin, which was demonstrated by means of electroimmunoassay and Northern blot analysis. This stimulation appeared to be on the level of transcription as shown in transient transfection experiments using various alpha-1-antichymotrypsin gene promoter constructs. In contrast to interleukin-6, virus-induced activation of the alpha-1-antichymotrypsin gene transcription does not require the STAT (signal transducers and activators of transcription) binding elements present in the alpha-1-antichymotrypsin gene promoter. Furthermore, alpha-amanitin, which inhibits eukaryotic RNA polymerase II and III, did not affect alpha-1-antichymotrypsin stimulation by the virus, indicating involvement of the viral transcriptional apparatus in transient activation of alpha-1-antichymotrypsin gene expression.
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PMID:Changes in alpha-1-antichymotrypsin expression in vaccinia virus infected HepG2 cells. 952 74

Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C reactive protein (CRP) and alpha-1-antichymotrypsin (ACT) in 145 patients with probable Alzheimer's disease (AD) and 51 non-demented controls were measured. To investigate the cellular activation of peripheral immune system, plasma levels of neopterin were also investigated. Plasma levels of IL-1 were detectable in 17 patients with AD (13%) and only in one control (2%) and average levels of IL-1 were higher in AD patients than in controls (p < 0.001). IL-6 plasma levels were detectable in a higher proportion of AD and controls (53% and 27%, respectively), and were increased in patients with AD (p < 0.001). Plasma levels of ACT were increased in patients with AD (p < 0.001) and CRP levels were in the normal range. Plasma levels of neopterin were slightly lower in AD patients than in controls, but differences were not statistically significant. No significant correlation was observed between IL-1 and IL-6 levels or neopterin and cytokine levels in plasma from AD patients. Plasma levels of ACT negatively correlated with cognitive performances, as assessed by the mini mental state examination (MMSE; R = -0.26, p < 0.02) and positively correlated with the global deterioration state (GDS) of AD patients (R = 0.30, p < 0.007). Present findings suggested that detectable levels of circulating cytokines and increased ACT might not be derived by activation of peripheral immune system of AD patients. Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD.
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PMID:Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? 1067 95

Neuroinflammation is a central feature of Alzheimer disease (AD). It involves an innate immune reaction of sufficient intensity that self attack on neurons occurs. This phenomenon is best described as autotoxicity to distinguish it from classical autoimmunity which involves cloning of peripheral lymphocytes. Many compounds have been identified in AD brain which are known to promote and sustain inflammatory responses. They include beta-amyloid protein; the pentraxins C-reactive protein and amyloid P; complement proteins; the inflammatory cytokines interleukin-1, interleukin-6 and tumor necrosis factor-alpha; the protease inhibitors alpha-2-macroglobulin and alpha-1-antichymotrypsin; and the prostaglandin generating cyclooxygenases COX-1 and COX-2. Orally effective agents which can counteract the influence of these inflammatory stimulators should be effective in treating AD. Epidemiological evidence, coupled with results from pilot clinical trials, suggest there is great promise for traditional COX-1 inhibiting NSAIDs. Inhibitors of mediators closer to the core processes might offer even greater therapeutic promise. Some theoretical opportunities are suggested, based on intervention in the action of the above mentioned mediators.
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PMID:Inflammation, autotoxicity and Alzheimer disease. 1175 86

The aim of the current study was to examine the association between homocysteine and 6-year cognitive decline, and the modifying role of the inflammatory markers Interleukin-6 (IL-6), C-reactive protein (CRP) and alpha-1-antichymotrypsin (ACT). Data were collected within the Longitudinal Aging Study Amsterdam (ages >or=65 years) and analyzed using multiple longitudinal regression models (N=1257 of whom N=1076 had longitudinal data). Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), Coding Task (information processing speed) and Raven Coloured Progressive Matrices (fluid intelligence). Higher homocysteine at baseline was negatively associated with prolonged lower cognitive functioning and a faster rate of decline in information processing speed and fluid intelligence. The negative association between higher homocysteine and immediate recall was strongest in persons with a high level of IL-6. Only in the highest tertile of CRP, higher homocysteine was negatively associated with retention. In the middle tertile of ACT, higher homocysteine was associated with lower information processing speed and faster decline. Both in the lower and middle tertile of CRP, higher homocysteine was associated with a faster rate of decline in information processing speed. The results implicate that a combination of both risk factors may be used as a marker for cognitive impairment.
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PMID:Homocysteine and inflammation: predictors of cognitive decline in older persons? 1900 29