scholarly journals Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

2013 ◽  
Vol 20 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Katherine H. Restori ◽  
Mary J. Kennett ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Expression Profiles ◽  
Cytokine Gene Expression ◽  
Dependent Manner ◽  
Pneumonia Severity ◽  
Content Type ◽  
Amyloid A

ABSTRACTVaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positiveStreptococcus pneumoniaeserotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.

scholarly journals Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, inhibits induction of acute-phase proteins by interleukin-6 alone or in combination with interleukin-1 in human hepatoma cell lines

1992 ◽  
Vol 284 (3) ◽  
pp. 645-648 ◽  
Author(s):  
M K Ganapathi
Keyword(s):  
Acute Phase ◽  
Okadaic Acid ◽  
Interleukin 6 ◽  
Acute Phase Proteins ◽  
Protein Phosphatases ◽  
Hepatoma Cell ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Amyloid A ◽  
20 Nm

Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, inhibited in a dose-dependent manner (5-20 nM) the induction of C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells. Induction of alpha 1-proteinase inhibitor (alpha 1-PI) by IL-6 plus IL-1 or IL-6 alone was not significantly affected by OA up to concentrations of 20 nM, above which concentration OA was toxic in Hep 3B cells. OA also inhibited the induction of CRP, fibrinogen and alpha 1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a higher concentration (80 nM). These results suggest that the signal transduction mechanisms regulating induction of acute-phase proteins by IL-6, either alone or in combination with IL-1, are mediated by activation of protein phosphatases 1 and/or 2A.

scholarly journals Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2

1995 ◽  
Vol 309 (2) ◽  
pp. 461-464 ◽  
Author(s):  
W Pruzanski ◽  
F C de Beer ◽  
M C de Beer ◽  
E Stefanski ◽  
P Vadas
Keyword(s):  
Phospholipase A2 ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Lipolytic Activity ◽  
Lipoprotein Metabolism ◽  
Serum Amyloid ◽  
Dependent Manner ◽  
Amyloid A ◽  
Serum Amyloid A Protein

The acute-phase proteins serum amyloid A protein (SAA) and secretory phospholipase A2 (sPLA2) are simultaneously expressed during inflammatory conditions. SAA associates with high-density lipoprotein (HDL) altering its physicochemical composition. We found that purified acute-phase SAA, but not the constitutive form, markedly enhances the lipolytic activity of sPLA2 in a dose-related manner with phosphatidylcholine/lysophosphatidylcholine or phosphatidylethanolamine/lysophosphatidylethanolamine liposomal substrates. Normal HDL was found to reduce activity of sPLA2 in a dose-dependent manner, but when acute-phase HDL containing 27% SAA was tested, it enhanced sPLA2 activity. Immunopurified monospecific antibodies against SAA completely abolished the enhancing activity of SAA and acute-phase HDL. Given the central role of HDL in lipoprotein metabolism, the interaction between HDL, SAA and sPLA2 may account for changes detected in lipoprotein metabolism during the acute phase.

scholarly journals Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Pavan K. Bhatraju ◽  
Eric D. Morrell ◽  
Leila Zelnick ◽  
Neha A. Sathe ◽  
Xin-Ya Chai ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Epithelial Cell ◽  
Acute Phase ◽  
Cell Injury ◽  
Acute Phase Proteins ◽  
Invasive Mechanical Ventilation ◽  
Icu Patients ◽  
Icu Admission ◽  
Amyloid A ◽  
Epithelial Cell Injury

Abstract Background Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. Methods We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. Results In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. Conclusions These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.

scholarly journals Effects of Stocking and Transport Conditions on Physicochemical Properties of Meat and Acute-Phase Proteins in Cattle

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 252
Author(s):  
Ahmed A. Abubakar ◽  
Idrus Zulkifli ◽  
Yong M. Goh ◽  
Ubedullah Kaka ◽  
Azad B. Sabow ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Stocking Density ◽  
Road Transport ◽  
Long Distance ◽  
Amyloid A ◽  
Tropical Conditions ◽  
Meat Samples ◽  
Water Holding

This study’s objective was to evaluate the effects of distance and stocking density on physicochemical properties and oxidative stability of meat and acute-phase proteins in Brahman crossbred cattle transported by road under hot and humid tropical conditions. Sixty Brahman crossbred heifers were subjected to road transport from a cattle feedlot farm located in Universiti Putra Malaysia (UPM), Serdang, to a commercial ruminant abattoir in Shah Alam, Selangor. Animals were assigned to long and short distances and high, medium, and low stocking densities. The results revealed that the intensity of response significantly increased in meat samples from animals subjected to long-distance transportation and higher stocking density. Alpha-1-acid glycoprotein and serum amyloid-A values increased considerably and were different from the baseline values recorded at preload. In conclusion, the current results revealed that the color, pH, shear force values, water holding capacity (WHC), glycogen level, and malondilaldehyde assay (MDA) concentrations in meat and acute-phase proteins (APP) were affected by both distances and stocking densities, as evidenced by the significant changes recorded from the parameters above.

scholarly journals Gene Expression and Transcriptome Profiling of Changes in a Cancer Cell Line Post-Exposure to Cadmium Telluride Quantum Dots: Possible Implications in Oncogenesis

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110198
Author(s):  
Mohammed S. Aldughaim ◽  
Mashael R. Al-Anazi ◽  
Marie Fe F. Bohol ◽  
Dilek Colak ◽  
Hani Alothaid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantum Dots ◽  
Cancer Cells ◽  
Cadmium Telluride ◽  
Cancer Progression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dependent Manner ◽  
Cdte Qds ◽  
Cadmium Telluride Quantum Dots

Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells. Chang cancer cells were treated with 2 different doses of CdTe-QDs (10 and 25 μg/ml) at different time intervals (6, 12, and 24 h). Functional annotations helped identify the gene expression profile in terms of its biological process, canonical pathways, and gene interaction networks activated. It was found that the gene expression profiles varied in a time and dose-dependent manner. Validation of transcriptional changes of several genes through quantitative PCR showed that several genes upregulated by CdTe-QD exposure were somewhat linked with oncogenesis. CdTe-QD-triggered functional pathways that appear to associate with gene expression, cell proliferation, migration, adhesion, cell-cycle progression, signal transduction, and metabolism. Overall, CdTe-QD exposure led to changes in the gene expression profiles of the Chang cancer cells, highlighting that this nanoparticle can further drive oncogenesis and cancer progression, a finding that indicates the merit of immediate in vivo investigation.

Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

2003 ◽  
Vol 95 (4) ◽  
pp. 1656-1663 ◽  
Author(s):  
C. A. Rivera ◽  
M. H. Tcharmtchi ◽  
L. Mendoza ◽  
C. W. Smith
Keyword(s):  
Acute Phase ◽  
Hepatic Injury ◽  
Acute Phase Proteins ◽  
Elevated Serum ◽  
Hindlimb Unloading ◽  
Low Grade ◽  
Systemic Blood ◽  
Blood Samples ◽  
Amyloid A ◽  
Organ Systems

Hindlimb unloading (HU) is known to induce physiological alterations in various organ systems that mimic some responses observed after exposure to microgravity. In the present study, the effects of up to 4 wk of HU on the liver were assessed in male Wistar rats and two mouse strains: endotoxin-sensitive C57BL/6 mice and endotoxin-resistant C3H/HEJ mice. Plasma levels of endotoxin, a known stimulator of hepatic injury, were measured in portal and systemic blood samples. Endotoxin was elevated by ∼50% in portal blood samples of mice and rats but was not detectable in systemic blood. This low-grade portal endotoxemia was associated with hepatic injury in rats and C57BL/6 mice as indicated by inflammation and elevated serum transaminase activities. Blood levels of the cytokine TNF-α were increased by ∼50% in C57BL/6 mice; no significant elevation of this cytokine was detected in rats. Messenger RNA levels of the acute-phase proteins serum amyloid A, haptoglobin, and lipopolysaccharide binding protein were significantly enhanced after 3 wk of HU in endotoxin-sensitive rodents. In contrast, no histological changes or significant increases in serum enzyme activity were detected after HU in C3H/HEJ mice despite portal endotoxin levels of 222 ± 83.4 pg/ml. At the 3-wk time point, expression of acute-phase proteins was not elevated in C3H/HEJ mice; however, expression after 4 wk of HU was similar to endotoxin-sensitive rodents. In conclusion, these findings indicate that HU induced mild portal endotoxemia, which contributed to the observed hepatic injury in endotoxin-sensitive rodents.

scholarly journals Serum Amyloid A Promotes Cholesterol Efflux Mediated by Scavenger Receptor B-I

2005 ◽  
Vol 280 (43) ◽  
pp. 35890-35895 ◽  
Author(s):  
Deneys R. van der Westhuyzen ◽  
Lei Cai ◽  
Maria C. de Beer ◽  
Frederick C. de Beer
Keyword(s):  
Acute Phase ◽  
Cholesterol Efflux ◽  
Serum Amyloid A ◽  
Acute Phase Protein ◽  
Scavenger Receptor ◽  
Dependent Manner ◽  
Cellular Cholesterol ◽  
Amyloid A ◽  
Phase Protein ◽  
Cellular Cholesterol Efflux

Serum amyloid A (SAA) is an acute phase protein whose expression is markedly up-regulated during inflammation and infection. The physiological function of SAA is unclear. In this study, we reported that SAA promotes cellular cholesterol efflux mediated by scavenger receptor B-I (SR-BI). In Chinese hamster ovary cells, SAA promoted cellular cholesterol efflux in an SR-BI-dependent manner, whereas apoA-I did not. Similarly, SAA, but not apoA-I, promoted cholesterol efflux from HepG2 cells in an SR-BI-dependent manner as shown by using the SR-BI inhibitor BLT-1. When SAA was overexpressed in HepG2 cells using adenovirus-mediated gene transfer, the endogenously expressed SAA promoted SR-BI-dependent efflux. To assess the effect of SAA on SR-BI-mediated efflux to high density lipoprotein (HDL), we compared normal HDL, acute phase HDL (AP-HDL, prepared from mice injected with lipopolysaccharide), and AdSAA-HDL (HDL prepared from mice overexpressing SAA). Both AP-HDL and AdSAA-HDL promoted 2-fold greater cholesterol efflux than normal HDL. Lipid-free SAA was shown to also stimulate ABCA1-dependent cholesterol efflux in fibroblasts, in line with an earlier report (Stonik, J. A., Remaley, A. T., Demosky, S. J., Neufeld, E. B., Bocharov, A., and Brewer, H. B. (2004) Biochem. Biophys. Res. Commun. 321, 936–941). When added to cells together, SAA and HDL exerted a synergistic effect in promoting ABCA1-dependent efflux, suggesting that SAA may remodel HDL in a manner that releases apoA-I or other efficient ABCA1 ligands from HDL. SAA also facilitated efflux by a process that was independent of SR-BI and ABCA1. We conclude that the acute phase protein SAA plays an important role in HDL cholesterol metabolism by promoting cellular cholesterol efflux through a number of different efflux pathways.

Variations in the levels of acute-phase proteins and lactoferrin in serum and milk during bovine subclinical mastitis

2021 ◽  
pp. 1-5
Author(s):  
Aarsha Raj ◽  
Vinodkumar Kulangara ◽  
Tresamol P. Vareed ◽  
Deepa P. Melepat ◽  
Latha Chattothayil ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Proteins ◽  
Solid Phase ◽  
Bovine Mastitis ◽  
Subclinical Mastitis ◽  
Clinical Mastitis ◽  
Reactive Protein ◽  
Amyloid A ◽  
California Mastitis Test ◽  
Bacterial Organism

Abstract Variations in the levels of acute phase proteins and lactoferrin in serum and milk for diagnosis of subclinical mastitis in dairy cows are described in this research paper. Milking animals from two organized dairy farms in Kerala, India, were screened by California Mastitis Test (CMT), Electrical Conductivity test (EC) and Somatic Cell Count (SCC) test to identify animals affected with sub clinical mastitis (SCM). The concentrations of acute phase proteins (APP) Haptoglobin (Hp), C- reactive protein (CRP), Albumin, Lactoferrin (Lf) and α- 1 acid glycoprotein (AGP) in milk and Hp, Albumin, Serum Amyloid A (SAA) and CRP in the serum of 40 normal cows and 40 cows affected with sub clinical mastitis were assessed. Solid phase ELISA was employed for assessment of all parameters except the albumin levels, for which spectrophotometry was used. The values of Hp in milk; and SAA, AGP and Lf in serum, were significantly elevated in the group with sub clinical mastitis. Such variations were found to be independent of the specific bacterial organism causing the disease. These results show that significant variations exist in the levels of acute phase proteins Hp, AGP and Lf in milk, and SAA in serum of animals affected with subclinical bovine mastitis that are not affected by specific bacterial etiology.

Stimulation of the acute-phase response in simian virus 40-hepatocyte cell lines

1989 ◽  
Vol 9 (7) ◽  
pp. 2779-2786
Author(s):  
W S Liao ◽  
K T Ma ◽  
C D Woodworth ◽  
L Mengel ◽  
H C Isom
Keyword(s):  
Cell Lines ◽  
Acute Phase ◽  
Molecular Mechanisms ◽  
Constitutive Expression ◽  
Simian Virus 40 ◽  
Normal Liver ◽  
Simian Virus ◽  
Cdna Clones ◽  
Dependent Manner ◽  
Amyloid A

Seven simian virus 40 (SV40)-hepatocyte cell lines were characterized with respect to the ability to express eight liver acute-phase genes. cDNA clones corresponding to albumin, serum amyloid A, alpha 1-acid glycoprotein, haptoglobin, alpha-, beta-, and gamma-fibrinogen, and alpha 1-major-acute-phase protein mRNAs were used in Northern (RNA) or slot blot analyses. In the noninduced state, six of the seven cell lines showed significant (i.e., liverlike) levels of constitutive expression of all genes examined except that expression of haptoglobin mRNA was considerable lower than in the normal liver. To examine whether these immortalized liver cells can respond appropriately to inflammatory mediators, cells were treated with conditioned medium from activated human monocytes or mixed lymphocyte cultures. Results showed that these SV40-hepatocyte cell lines responded to the conditioned media in culture by down-regulating albumin gene expression and up-regulating other acute-phase genes in a time- and dose-dependent manner. These results indicate that the SV40-hepatocytes retained not only the ability to express a number of acute-phase genes but also the ability to respond to external stimuli. The usefulness of these cell lines for analysis of the molecular mechanisms involved in the regulation of these acute-phase genes is discussed.

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