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 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 Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1851-1854
Author(s):  
F Benigni ◽  
G Fantuzzi ◽  
S Sacco ◽  
M Sironi ◽  
P Pozzi ◽  
...  
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Serum Amyloid A ◽  
Acute Phase Protein ◽  
Interleukin 1 ◽  
Serum Corticosterone ◽  
Amyloid A ◽  
Phase Protein ◽  
Hypothalamus Pituitary Adrenal Axis ◽  
Pituitary Adrenal Axis

Ciliary neurotrophic factor (CNTF) and interleukin-6 (IL-6) potentiate the elevation of serum corticosterone induced by suboptimal doses of interleukin-1 (IL-1). CNTF also potentiates IL-1-induced serum IL-6. Here, we report that four other cytokines (leukemia inhibitory factor [LIF], oncostatin M [OSM], interleukin-11 and cardiotrophin-1) also potentiated the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, all the six cytokines studied induced the acute-phase protein serum amyloid A when administered alone. Because these cytokines differ both in structure and in function, but share gp130 as a subunit of their receptors, these results indicate that signaling through gp130 mediates potentiation of IL-1 activities. The potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. In fact, in IL-6 deficient mice, IL-1 increased serum corticosterone to a level comparable to that observed in wild-type mice. Thus, either endogenous IL-6 does not mediate IL-1-induced corticosterone increase, or its role may be fulfilled by other cytokines. To the extent that gp130-dependent cytokines may serve this role, they may be important feedback regulators of inflammation through the activation of the hypothalamus-pituitary-adrenal axis and the potentiation of acute-phase protein synthesis.

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 Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1851-1854 ◽  
Author(s):  
F Benigni ◽  
G Fantuzzi ◽  
S Sacco ◽  
M Sironi ◽  
P Pozzi ◽  
...  
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Serum Amyloid A ◽  
Acute Phase Protein ◽  
Interleukin 1 ◽  
Serum Corticosterone ◽  
Amyloid A ◽  
Phase Protein ◽  
Hypothalamus Pituitary Adrenal Axis ◽  
Pituitary Adrenal Axis

Abstract Ciliary neurotrophic factor (CNTF) and interleukin-6 (IL-6) potentiate the elevation of serum corticosterone induced by suboptimal doses of interleukin-1 (IL-1). CNTF also potentiates IL-1-induced serum IL-6. Here, we report that four other cytokines (leukemia inhibitory factor [LIF], oncostatin M [OSM], interleukin-11 and cardiotrophin-1) also potentiated the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, all the six cytokines studied induced the acute-phase protein serum amyloid A when administered alone. Because these cytokines differ both in structure and in function, but share gp130 as a subunit of their receptors, these results indicate that signaling through gp130 mediates potentiation of IL-1 activities. The potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. In fact, in IL-6 deficient mice, IL-1 increased serum corticosterone to a level comparable to that observed in wild-type mice. Thus, either endogenous IL-6 does not mediate IL-1-induced corticosterone increase, or its role may be fulfilled by other cytokines. To the extent that gp130-dependent cytokines may serve this role, they may be important feedback regulators of inflammation through the activation of the hypothalamus-pituitary-adrenal axis and the potentiation of acute-phase protein synthesis.

scholarly journals Investigation of the Effect of Tarantula cubensis Extract on Acute Phase Response

2018 ◽  
Vol 44 (1) ◽  
pp. 5
Author(s):  
Orhan Corum ◽  
Ayse Er ◽  
Burak Dik
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Acute Phase Proteins ◽  
Interleukin 1 ◽  
Alcoholic Extract ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Background: Tarantula cubensis alcoholic extract is used to accelerate wound healing and to relieve edema in many animal species. In addition, it may be useful for many infectious diseases. Considering to these effects, it is believe that these effects may be on immune system. Cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma) secreted by immune cells and acute phase proteins (haptoglobin, alpha 1 acid glycoprotein, serum amyloid A) secreted by liver play role in acute phase response. The aim of the present study was to determine the effect of Tarantula cubensis alcoholic extract on cytokine and acute phase protein levels in sheep.Materials, Methods & Results: Tarantula cubensis alcoholic extract (6 mL/sheep, subcutaneously, single dose) was administered to 6 healthy sheep. Blood samples were obtained before (0 h) and after treatments at 2, 4, 8, 12, 24 and 48 h. Then, blood samples were centrifuged to obtain serum samples. Acute phase cytokines such as serum tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma and acute phase proteins such as haptoglobin, alpha 1 acid glycoprotein and serum amyloid-A concentrations were determined with commercially available kits on ELISA reader. Administration of Tarantula cubensis alcoholic extract caused fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma levels in sheep. In addition, levels of haptoglobin, alpha 1 acid glycoprotein, serum amyloid A showed fluctuations. But, these fluctuations in acute phase cytokines and acute phase proteins were not statistically significant (P > 0.05).Discussion: Tarantula cubensis alcoholic extract, homeopathic medicine, is used trauma, retentio secundinarium, tendinitis, bluetongue, foot and mouth, metritis and arthritis in many animal species including sheep. Cytokines, secreted against various stimulus including infectious diseases, play role in wound healing and in the regulation of the immune system. In current study, administration of Tarantula cubensis alcoholic extract lead to fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma levels, but these changes were not statistically significant (P > 0.05). Non-statistical fluctuations in cytokines result from inadequate immunological response of sheep against to Tarantula cubensis alcoholic extract. Also, use of molecular analysis techniques may be changed these results. Acute phase proteins are significantly secreted from the liver during the acute phase response. In current study, administration of Tarantula cubensis alcoholic extract in sheep caused non-statistifical fluctuations on haptoglobin, alpha 1 acid glycoprotein and serum amyloid A levels (P > 0.05). Tumor necrosis factor alpha and interleukin-1 beta stimulate synthesis of interleukin-6. Interleukin-6 provides synthesis of acute phase proteins in liver. Non-statistical fluctuations in acute phase proteins result from inadequate stimulus of IL-6. In conclusion, it may be stated that administration of Tarantula cubensis alcoholic extract has no distinctive effect on the acute phase response. However, when Tarantula cubensis alcoholic extract is administered repeated times or other acute phase parameters are evaluated, different results may be observed.

scholarly journals Inhibition of Acute Phase Inflammation byLaminaria japonicathrough Regulation of iNOS-NF-κB Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Seong Kyu Park ◽  
Sook Jahr Park ◽  
Sang Mi Park ◽  
Il Je Cho ◽  
Chan Ik Park ◽  
...  
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Laminaria Japonica ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Paw Edema ◽  
Edema Formation ◽  
Concentration Dependent Manner ◽  
Cox 2

Laminaria japonicahas been frequently used as food supplements in many of the Asian countries and as a drug in traditional oriental medicine. This research investigated the effects ofLaminaria japonicaextract (LJE) on acute phase inflammation in a carrageenan-induced paw edema model, as assessed by histomorphometric and immunohistochemical analyses. The effect of LJE was also evaluated in Raw264.7 cells stimulated with lipopolysaccharide (LPS) in the aspect of the inhibition of nitric oxide (NO), prostaglandin E2(PGE2), and proinflammatory cytokines production. NO, PGE2, tumor necrosis factor (TNF)-α, interleukin-1β, and interleukin-6 contents were assayed by ELISA, and inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expressions were determined by western blot analyses. In rats, LJE treatment inhibited carrageenan-induced paw edema formation and infiltration of inflammatory cells in H&E staining. LJE treatment prevented the ability of LPS to increase the levels of iNOS and COX-2 protein in a concentration-dependent manner. Consistently, LJE suppressed the production of TNF-α, interleukin-1β, and interleukin-6. Treatment of the cells with LJE caused inhibition of inhibitor ofκBαphosphorylation induced by LPS, suggesting LJE repression of nuclear factor-κB activity by LPS. In conclusion, this study shown here may be of help to understand the action mechanism of LJE and the anti-inflammatory use ofL. japonica.

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.

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