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Acute Phase Proteins (acute + phase_protein)

Distribution by Scientific Domains

Medical Sciences	66%
Chemistry	20%
Life Sciences	13%

Selected Abstracts

CYTOKINES AND ACUTE PHASE PROTEINS AS MARKERS FOR INFECTION IN HARBOR PORPOISES (PHOCOENA PHOCOENA)

MARINE MAMMAL SCIENCE, Issue 4 2007
S. Fonfara
First page of article [source]

The PPAR, agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2007
T. Kino
Abstract Background, Interleukin-6 and downstream liver effectors acute phase reactants are implicated in the systemic inflammatory reaction. Peroxisome proliferator-activated receptor , (PPAR,), which binds to and is activated by a variety of fatty acids, was recently shown to have anti-inflammatory actions. Materials and methods, We examined the ability of the synthetic PPAR, agonist GW501516 to suppress interleukin-6-induced expression of acute phase proteins in human hepatoma HepG2 cells and rat primary hepatocytes. Results, GW501516 dose-dependently suppressed interleukin-6-induced mRNA expression of the acute phase protein ,1-antichymotrypsin in HepG2 cells. The compound also suppressed interleukin-6-induced mRNA expression of ,2-acid glycoprotein, ,-fibrinogen and ,2-macroglobulin in and the secretion of C-reactive protein by rat primary hepatocytes. Depletion of the PPAR, receptor, but not of PPAR, or ,, attenuated the suppressive effect of GW501516 on interleukin-6-induced ,1-antichymotrypsin mRNA expression, indicating that PPAR, specifically mediated this effect. Since interleukin-6 stimulates the transcriptional activity of the ,1-antichymotrypsin promoter by activating the signal transducer and activator of transcription (STAT) 3, we examined functional interaction of this transcription factor and PPAR, on this promoter. Overexpression of PPAR, enhanced the suppressive effect of GW501516 on STAT3-activated transcriptional activity of the ,1-antichymotrypsin promoter, while GW501516 suppressed interleukin-6-induced binding of this transcription factor to this promoter. Conclusions, These findings indicate that agonist-activated PPAR, interferes with interleukin-6-induced acute phase reaction in the liver by inhibiting the transcriptional activity of STAT3. PPAR, agonists might be useful for the suppression of systemic inflammatory reactions in which IL-6 plays a central role. [source]

Hepatocyte nuclear factor-4, interacts with other hepatocyte nuclear factors in regulating transthyretin gene expression

FEBS JOURNAL, Issue 19 2010
Zhongyan Wang
Transthyretin is a negative acute phase protein whose serum level decreases during the acute phase response. Transthyretin gene expression in the liver is regulated at the transcriptional level, and is controlled by hepatocyte nuclear factor (HNF)-4, and other HNFs. The site-directed mutagenesis of HNF-4, HNF-1, HNF-3 and HNF-6 binding sites in the transthyretin proximal promoter dramatically decreases transthyretin promoter activity. Interestingly, the mutation of the HNF-4 binding site not only abolishes the response to HNF-4,, but also reduces significantly the response to other HNFs. However, mutation of the HNF-4 binding site merely affects the specific binding of HNF-4,, but not other HNFs, suggesting that an intact HNF-4 binding site not only provides a platform for specific interaction with HNF-4,, but also facilitates the interaction of HNF-4, with other HNFs. In a cytokine-induced acute phase response cell culture model, we observed a significant reduction in the binding of HNF-4,, HNF-1,, HNF-3, and HNF-6, to the transthyretin promoter, which correlates with a decrease in transthyretin expression after injury. These findings provide new insights into the mechanism of the negative transcriptional regulation of the transthyretin gene after injury caused by a decrease in the binding of HNFs and a modulation in their coordinated interactions. [source]

Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system,

HEPATOLOGY, Issue 6 2006
Muriel Lavie
Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity. (HEPATOLOGY 2006;44:1626,1634.) [source]

The acute phase protein haptoglobin is locally expressed in arthritic and oncological tissues

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2003
Mirjam B. Smeets
Summary., Haptoglobin is an acute phase protein known to be highly expressed in the liver. Recently, we showed increased local arterial haptoglobin expression after flow-induced arterial remodelling and found that haptoglobin is involved in cell migration and arterial restructuring probably through accumulation of a temporary gelatin matrix. Since cell migration and matrix turnover are important features in the pathology of arthritis and cancer, we hypothesized that haptoglobin is also locally expressed in arthritic and oncological tissues. In this study, we investigated local haptoglobin expression in arthritic rats (n = 12) using semi-quantitative PCR and Western blotting, and we studied haptoglobin mRNA localization in human kidney tumours (n = 3) using in situ hybridization. The arthritic rats demonstrated an increase of haptoglobin mRNA (2.5-fold, P < 0.001) and protein (2.6-fold, P < 0.001) in the arthritic Achilles tendon. Haptoglobin protein was also increased in the arthritic ankle (2.6-fold, P < 0.001) but not in the non-arthritic knee. In human kidney tumours, tumour and stromal cells produced haptoglobin mRNA. This study shows that the liver protein haptoglobin is, in addition to the artery, also expressed in arthritic and oncological tissues that are recognized for enhanced cell migration and matrix turnover. [source]

Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome: implications,

JOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 6 2000
J. A. Tsiouris
Abstract Studies of immune function during depression in persons without intellectual disability (ID) have revealed elevated levels of ,2 macroglobulin (,2M) and an acute phase protein (APP) response. Clinical observation suggests that people with Down's syndrome (DS) may have associated genetic abnormalities in their immune systems. The APP response and ,2M changes in depressed versus non-depressed adults with DS was the subject of the present study. The serum pan-proteinase inhibitor ,2M, and the AP proteins c-reactive protein (CRP), ,1 antitrypsin (,1AT), ceruloplasmin (Cp), ,2 Macroglobulin (,2M), transthyretin (Trans), serum amyloid protein (SAP), and albumin (Alb) were measured in 38 adults with DS, 19 of whom were diagnosed with and 19 without depression using a sandwich enzyme-linked immunosorbent assay (ELISA). The DSM-IV criteria were used for diagnoses. Medical and neurological examinations excluded medical disorders associated with APP response. Only ,2M and CRP were significantly different in the depressed versus non-depressed groups. The ,2M was higher, a response similar to one observed in depressed people without ID, but the CRP was lower in the depressed group, especially in those subjects not on psychotropic medications, contrary to the expected APP response to depression. The results suggest that ,2M elevation in depressed adults with DS is independent of the APP response. An alternative explanation for its elevation is proposed linking the core symptom of depression with the mammalian dormancy/hibernation process. Further studies are needed to confirm that ,2M elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID. [source]

C-reactive protein and coronary heart disease: a critical review

JOURNAL OF INTERNAL MEDICINE, Issue 4 2008
J. P. Casas
Abstract. Modestly elevated baseline concentrations of C-reactive protein (CRP), the classical acute phase protein, are associated with the long-term risk of coronary heart disease in general populations, whilst the major acute phase response of CRP following myocardial infarction is associated with death and cardiac complications. The pathogenic and clinical significance of these associations is controversial. Here we critically review the evidence and describe large-scale epidemiological studies, novel experiments and possible specific therapies which will rigorously inform the debate. We distinguish between the potential pathogenicity of high acute phase circulating CRP concentrations in individuals with substantial tissue damage and modest but persistent increases in baseline values in generally healthy subjects. [source]

The birth process initiates an acute phase reaction in the fetus-newborn infant

ACTA PAEDIATRICA, Issue 9 2000
G Marchini
Our goal was to investigate whether the normal birth process stimulated an acute phase response in healthy infants with physiological changes in the circulating levels of acute phase cytokines and acute phase proteins. We also monitored body temperature, body weight and behavioural state in order to investigate if clinical signs of acute phase reaction were present. We made cross-sectional measurements of interleukin-1,, interleukin-6, C-reactive protein, serum amyloid A, procalcitonin, prealbumin, body weight, body temperature and the duration of the sleeping period during the first four postnatal days. We found an increase in interleukin-6 (p < 0.001) during the first day, followed by an increase in C-reactive protein, serum amyloid A and procalcitonin on the second postnatal day (p < 0.01). The level of prealbumin fell after birth and reached its lowest value at 3 d of age (p < 0,001). Interleukin-l p remained unchanged. The duration of the sleeping period was longer during the first day (p < 0.01). There was an increase in body temperature during the first day (p < 0.01). Maximal weight loss was during the first 2 d. Conclusions: The normal birth process and extra-uterine adaptation stimulates an acute phase reaction in the newborn infant with a release of interleukin-6 and acute phase proteins and a depression of prealbumin. This reaction, as the body's first line inflammatory defence system, probably affects the infant's behaviour, nutritional state as well as the regulation of body temperature. [source]

The PPAR, agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition

The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses

IMMUNOLOGICAL REVIEWS, Issue 1 2000
Shuhji Seki
Summary: The liver remains a hematopoietic organ after birth and can produce all leukocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipopolysaccharide (LPS) and bacterial superantigens, and produce interleukin (IL)-12. IL-12 and other monokines (IL-18 etc.) produced by Kupffer cells activate liver natural killer (NK) cells and NK1.1 Ag+ T cells to produce interferon-g and thereby acquire cytotoxicity against tumors and microbe-infected cells. These liver leukocytes and the T helper 1 immune responses induced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this defense system is inadequately activated, shock associated with multiple organ failure takes place. Activated liver NK1.1 Ag+ T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ T cells and another T-cell subset with an intermediate T-cell receptor, CD122+CD8+ T cells, can develop independently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells physiologically develop in situ from their precursors, presumably due to bacterial antigens brought from the intestine via the portal vein. NK cells activated by bacterial superantigens or LPS are also probably involved in the vascular endothelial injury in Kawasaki disease. [source]

Cytokines alter the expression and activity of the multidrug resistance transporters in human hepatoma cell lines; analysis using RT-PCR and cDNA microarrays

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2003
Gigi Lee
Abstract Pro-inflammatory cytokines suppress the hepatic expression of the multidrug resistance transporters in rodents, indicating potential usefulness in chemotherapy. Our objective was to investigate their impact in human hepatoma cells. HuH 7 and HepG2 cells were treated with IL-1,, IL-6, or TNF-, for 0,72 h. Expression and activity of MDR1 and the MRP (MRP1, 2, 3, and 6) transporters were examined by RT-PCR, efflux assays, and microarrays. Significant reductions in the MDR1-mediated efflux of Rhodamine 123 and MDR1 mRNA levels were observed in HuH 7 cells treated with IL-6, TNF-,, or IL-1, and in TNF-,,treated HepG2 cells. However, cytokine-treated HuH7 cells also demonstrated 1.6- to 2.6-fold greater efflux of the MRP substrate, 5-carboxyfluorescein (5-CF) and higher MRP3 mRNA levels (p,<,0.05). IL-1, and IL-6 treatments increased MRP activity and MRP1 mRNA levels in HepG2 cells (p,<,0.05). Microarrays studies performed in IL-6 and TNF-,,treated HepG2 cells detected similar changes in the expression of the MDR1 and MRP transporters, but this did not reach significance. However, the microarrays confirmed cytokine-mediated induction of several acute phase proteins. Our data suggests that although cytokine-mediated suppression of PGP may alter drug resistance in malignant cells, these cytokines may also impose an induction in other multidrug resistance genes. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2152,2163, 2003 [source]

Steroid Responsive Meningitis-Arteritis: A Prospective Study of Potential Disease Markers, Prednisolone Treatment, and Long-Term Outcome in 20 Dogs (2006,2008)

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2009
M. Lowrie
Background: Previous multidrug studies have identified the value of prednisolone in treating steroid responsive meningitis-arteritis (SRMA) and the potential value of acute phase proteins (APPs) and immunoglobulin A (IgA) in diagnosis and monitoring. Hypothesis: (1) Prednisolone monotherapy is a successful immunosuppressive modality in the treatment of SRMA; (2) protein markers are useful in identifying the potential for relapse. Animals: Twenty client-owned dogs with SRMA presented to the University of Glasgow Small Animal Hospital between May 2006 and May 2008. Methods: A prospective, observational study: CBC, biochemistry, and cerebrospinal fluid (CSF) analyses were performed. C-reactive protein (CRP), serum amyloid-A, ,-1-acid glycoprotein, and haptoglobin (Hp) were assessed in the serum. IgA concentrations were determined in the serum and CSF. Results: Clinical resolution of SRMA was achieved in all 20 dogs. Serum CRP concentration remained increased at remission in 16/20 dogs whereas CSF cytology was within normal limits in 20/20 dogs. Serum APPs decreased significantly on treatment (P < .05) except Hp, which remained unaltered. Serum and CSF IgA concentrations remained increased for the duration of treatment. Conclusions and Clinical Importance: The prednisolone regimen presented was successful in treating SRMA without the need for additional drugs. Serum APPs are of use in the diagnosis and management of SRMA, particularly in relation to identifying relapse. Serum and CSF IgA concentrations remain increased throughout disease, aiding in diagnosis but not contributing to the management of SRMA. [source]

Carotid intima,media thickness in children and young adults with renal transplant: Internal carotid artery vs. common carotid artery

PEDIATRIC TRANSPLANTATION, Issue 8 2007
Yelda Bilginer
Abstract:, Cardiovascular diseases are the main causes of morbidity and mortality following renal transplantation. Atherosclerotic structural changes, which can be detected by high-resolution B-mode ultrasonography, begin before clinical findings. However, little is known about the extent of these abnormalities in children after renal transplantation. We aimed to determine early structural changes of large arteries in renal transplant recipients without cardiovascular disease and to evaluate the role of clinical and laboratory features on IMT of carotid arteries. IMT and hemoglobin, serum levels of creatinine, acute phase proteins, lipid profile, and homocysteine were examined in 24 asymptomatic renal transplant recipients (median age 16.5 yr; range 8,25), and 20 healthy controls (median age 16 yr; range 9,24). CCA and ICA were evaluated in patients and controls with a high-resolution B-mode ultrasonography in multiple projections to optimize detection of carotid IMT. Measurement of IMT of both CCA [0.36 mm (range 0.16,0.48) vs. 0.28 mm (range 0.21,0.35), p < 0.001] and ICA [0.27 mm (range 0.16,0.48) vs. 0.22 mm (range 0.1,0.26), p < 0.001] were significantly higher in renal recipients than in healthy controls. Among several parameters assessed, only significant correlations were found between duration of CRF, duration of dialysis prior to transplantation and ICA-IMT (p = 0.06 and p = 0.02, respectively) and between mean past serum calcium,phosphorus ion product and CCA-IMT (p = 0.002). In conclusion, our observations indicate that vascular changes begin early in the course of CRF and are directly related to time on CRF and dialysis. These changes can be detected by measuring CCA/ICA-IMT ultrasonographically. We suggest that early renal transplantation can potentially avoid long-term cardiovascular events in children with end stage kidney disease. [source]

2-D DIGE and MS/MS analysis of protein serum expression in rats housed in concrete and clay cages in winter

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 17 2008
Jong-Choon Kim
Abstract In a previous study, we examined the physiological responses of male Sprague,Dawley rats over a 4-week exposure to concrete and clay cages. No general toxicological changes were observed in rats exposed to either of the two cage types in summer. Under winter conditions, however, various general toxicological effects were detected in rats housed in concrete cages, although rats housed in clay cages showed no such effects. The infrared thermographic examination indicated that skin temperature in the concrete-housed rats was abnormally low, but not so in the clay-housed rats. We examined proteomic changes in the serum of rats housed in winter in concrete and clay cages using two-dimensional differential in-gel electrophoresis and mass spectrometry/mass spectrometry. Five proteins were identified and quantitatively validated; all were cold stress-induced, acute phase proteins that were either up-regulated (haptoglobin) or down-regulated (alpha-1-inhibitor III, alpha-2u globulin, complement component 3, and vitamin D-binding protein) in the concrete-housed rats. These results suggest that the 4-week exposure to a concrete cage in winter elicited a typical systemic inflammatory reaction (i.e. acute phase response) in the exposed rats. [source]

MS characterization of apheresis samples from rheumatoid arthritis patients for the improvement of immunoadsorption therapy , a pilot study

PROTEOMICS - CLINICAL APPLICATIONS, Issue 7 2009
Mike Kienbaum
Abstract Identification of proteins from apheresis samples was performed by both SDS-PAGE and 2-D gel separation of eluted proteins from staphylococcal protein A-based immunoadsorption columns (Prosorba®) followed by MS peptide mass fingerprinting and MS/MS peptide sequencing on a MALDI QIT TOF mass spectrometer. MS/MS peptide sequencing was performed in conjunction with a micro reversed phase HPLC configured with an online MALDI plate-spotting device. Apheresis treatment had been performed in three patients with longstanding therapy refractory rheumatoid arthritis. 2-D gels displayed ca. 500 spots representing proteins that were eluted from the Prosorba® columns. From 54 gels, a total of 1256 protein spots had been picked and yielded in the identification of 56 non-redundant proteins without counting isoforms. Proteins from the eluates belong to five major groups comprising (i) immunoglobulins (IgG, IgA, IgM heavy and light chains; about 40% of the spots), (ii) proteins involved in coagulation, (iii) HDL/LDL-associated proteins, (iv) proteins from the complement system, and (v) acute phase proteins. MS analysis showed that the full-length C3 complement protein had been cleaved upon complement activation, presumably on the column, such that the anaphylatoxin C3a was produced and released during therapy. Our results are consistent with clinical observations on both patient responses to therapy and reported adverse events. For the first time, direct molecular information has become available to support mechanistic reasoning for the principle of function of staphylococcal protein A-based immunoadsorption therapy and for the explanation of adverse events. According to our results, removal and/or modulation of immune complexes together with complement activation can be regarded as the major events that are taking place during Prosorba® therapy. In order to avoid complement activation and induction of an inflammatory cascade, we suggest the prevention of C3a anaphylatoxin-related reactions during immunoadsorption therapy. [source]