scholarly journals Human inter-α-inhibitor family in inflammation: simultaneous synthesis of positive and negative acute-phase proteins

1993 ◽  
Vol 292 (2) ◽  
pp. 485-492 ◽  
Author(s):  
M Daveau ◽  
P Rouet ◽  
M Scotte ◽  
L Faye ◽  
M Hiron ◽  
...  
Keyword(s):  
Acute Phase ◽  
Plasma Proteins ◽  
Acute Phase Proteins ◽  
Interleukin 1 ◽  
Acute Infection ◽  
Liver Biopsies ◽  
Simultaneous Synthesis ◽  
Quantitative Changes

The inter-alpha-inhibitor (I alpha I) family encompasses four plasma proteins, namely free bikunin as well as I alpha I, pre-alpha-inhibitor (P alpha I) and inter-alpha-like inhibitor (I alpha LI). Each of the last three proteins is a distinct assembly of one bikunin chain with one or more unique heavy (H) chains designated H1, H2 and H3. The three H chains and the bikunin chain are encoded by four distinct mRNAs. These molecules and chains, as well as the corresponding mRNAs, were quantified in sera and liver biopsies from a series of patients with or without mild or severe acute infection. The decrease or increase observed for a given molecule or chain in the serum was in agreement with a similar change in the corresponding liver mRNA. In acute inflammation the H2 and bikunin chains are down-regulated and the relevant molecules (I alpha I, I alpha LI) behave as negative acute-phase proteins, whereas the H3 chain is up-regulated and the corresponding P alpha I molecule is a positive acute-phase protein. Also, P alpha I displays a higher-than-usual M(r); this is probably due to ligand binding. The H1 gene does not seem to be affected by the inflammatory condition. The quantitative changes in RNA levels seen in vivo were confirmed in vitro in the human hepatoma Hep3B cell line prior to or after induction with the acute-phase mediators interleukin-1 and/or -6. These results provide the first example in humans of positive and negative acute-phase proteins that are encoded by evolutionary related genes.

Endotoxin-stimulated production of rat hypothalamic interleukin-1β in vivo and in vitro, measured by specific immunoradiometric assay

1993 ◽  
Vol 11 (1) ◽  
pp. 31-36 ◽  
Author(s):  
P Hagan ◽  
S Poole ◽  
A F Bristow
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Interleukin 1 ◽  
Phase Response ◽  
Inflammatory Stimuli ◽  
Quantitative Immunoassay ◽  
Time Courses ◽  
A Site

ABSTRACT Regulation of a number of aspects of the acute-phase response, including induction of fever and activation of the hypothalamo-pituitary-adrenal axis, occurs within the hypothalamus. The acute-phase response appears to be co-ordinated by the inflammatory cytokine interleukin-1 (IL-1). A number of studies using hybridization techniques to measure IL-1 gene expression and immunocyto-chemistry to localize immunoactive IL-1 have established the concept that the central nervous system, and in particular the hypothalamus, is a site of IL-1 production, and that levels increase in response to inflammatory stimuli. In this report we present data on the levels of IL-1β produced in the rat hypothalamus using quantitative immunoassay techniques. Bacterial endotoxin, administered to rats in vivo, evoked increases in hypothalamic IL-1β levels which were significant within 1 h, and reached maximum levels at 5–10 h. The response to endotoxin was dose-related, and levels reached in hypothalamic extracts corresponded to intra-hypothalamic levels of the order of 20 ng/ml. During short-term in-vitro culture of rat hypothalami, endotoxin stimulated a dose-related increase in both the synthesis and the secretion of IL-1β, which reached similar levels to those seen after in-vivo stimulation. Hypothalami obtained from animals stimulated with endotoxin in vivo did not, however, show any evidence of persistent stimulation of IL-1β production when subsequently cultured in vitro. These data support the concept that production of hypothalamic IL-1 is an essential step in regulating the activity of the hypothalamus during the acute-phase response, and provide for the first time quantitative data on the magnitude, dose—response relationships and time-courses of rat hypothalamic IL-1β production in vivo and in vitro.

scholarly journals Acute-phase protein synthesis: a key feature of innate immune functions of the liver

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christian Ehlting ◽  
Stephanie D. Wolf ◽  
Johannes G. Bode
Keyword(s):  
Acute Phase ◽  
Acute Phase Proteins ◽  
Protein Composition ◽  
Systemic Circulation ◽  
Central Component ◽  
Immune Functions ◽  
Main Site ◽  
And Function

Abstract The expression of acute-phase proteins (APP’s) maintains homeostasis and tissue repair, but also represents a central component of the organism’s defense strategy, especially in the context of innate immunity. Accordingly, an inflammatory response is accompanied by significant changes in the serum protein composition, an aspect that is also used diagnostically. As the main site of APP synthesis the liver is constantly exposed to antigens or pathogens via blood flow, but also to systemic inflammatory signals originating either from the splanchnic area or from the circulation. Under both homeostatic and acute-phase response (APR) conditions the composition of APP’s is determined by the pattern of regulatory mediators derived from the systemic circulation or from local cell populations, especially liver macrophages. The key regulators mentioned here most frequently are IL-1β, IL-6 and TNF-α. In addition to a variety of molecular mediators described mainly on the basis of in vitro studies, recent data emphasize the in vivo relevance of cellular key effectors as well as molecular key mediators and protein modifications for the regulation and function of APP’s. These are aspects, on which the present review is primarily focused.

scholarly journals The influence of glucocorticoid on the fibrinogen messenger RNA content of rat liver in vivo and in hepatocyte suspension culture

1984 ◽  
Vol 220 (3) ◽  
pp. 631-637 ◽  
Author(s):  
H M G Princen ◽  
H J Moshage ◽  
H J W de Haard ◽  
P J van Gemert ◽  
S H Yap
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Messenger Rna ◽  
Acute Phase Proteins ◽  
Rat Hepatocytes ◽  
Phase Response ◽  
Control Value ◽  
Hepatocyte Suspension

The plasma concentration of fibrinogen, one of the major acute-phase proteins produced by the liver, increases during the acute-phase response as a result of enhanced synthesis in liver. Since adrenal-cortical hormones have been thought to have a key role in the regulation of the fibrinogen synthesis, fibrinogen-polypeptide mRNA sequences were determined in the present study, by using a specific complementary-DNA probe, in RNA fractions obtained from rat hepatocytes exposed to glucocorticoids in vitro (hepatocyte suspension cultures) and in vivo. Maximal induction of the fibrinogen-polypeptide mRNA (to 400% of the control value) was found in vitro at 0.1 microM-dexamethasone after 9 h of incubation. The same magnitude of induction was obtained with 20 microM-cortisol or 60 microM-corticosterone. In contrast with the findings in vitro, no induction of the fibrinogen-polypeptide mRNA was observed in the liver at various times after injection of different doses of glucocorticoids into rats. These results suggest that more complex regulatory mechanisms are involved and that glucocorticoids are not the sole regulatory factors in vivo in the enhanced synthesis of fibrinogen during the acute-phase response.

Prostaglandins E2 and F2α are not involved in the monocytic-product (interleukin-1)-induced stimulation of hepatic fibrinogen synthesis in rats

1988 ◽  
Vol 74 (5) ◽  
pp. 477-483 ◽  
Author(s):  
J. C. W. M. Holtslag ◽  
H. J. Moshage ◽  
J. F. van Pelt ◽  
J. A. G. M. Kleuskens ◽  
F. W. J. Gribnau ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Second Messengers ◽  
Interleukin 1 ◽  
Rat Hepatocytes ◽  
Phase Response ◽  
Mrna Content ◽  
Stimulation Of

1. Monocytic products, especially interleukin-1 (IL-1), play an important role in the acute-phase response. Prostaglandins have been shown to act as second messengers in several physiological alterations of the acute-phase response, such as fever, muscle wasting and immunoregulation. The present study was undertaken to determine the role of prostaglandins in the monocytic-product-induced stimulation of the hepatic synthesis of fibrinogen, a well-known acute-phase protein. 2. Prostaglandin (PG) E2, PGF2α and 16,16-dimethyl-PGE2 did not stimulate fibrinogen synthesis and fibrinogen polypeptide mRNA content when administered intraperitoneally to rats or when added to monolayer cultures of rat hepatocytes. 3. Cyclo-oxygenase inhibitors did not abolish the stimulation of fibrinogen synthesis and its mRNA content induced by monocytic products in vivo or in vitro. 4. These findings indicate that the enhanced synthesis of fibrinogen induced by monocytic products (including IL-1) during the acute-phase response is not mediated by prostaglandins or other products of the cyclo-oxygenase pathway of arachidonic acid.

scholarly journals CHANGES PRODUCED IN MOUSE PLASMA PROTEINS BY ACUTE BACTERIAL INFECTIONS

1961 ◽  
Vol 114 (3) ◽  
pp. 311-325 ◽  
Author(s):  
Curtis A. Williams ◽  
Courtney T. Wemyss
Keyword(s):  
Plasma Proteins ◽  
Bacterial Infections ◽  
Acute Infection ◽  
Laboratory Animals ◽  
Striking Increase ◽  
Acute Infections ◽  
Hospital Patients ◽  
Acute Bacterial Infections

The immunoelectrophoretic patterns of plasma proteins from mice are altered significantly by acute infections. Some proteins are dissociated into two or more components, some showed striking increase in plasma concentration, others are depleted, and certain ones appear which are undetectable in normal samples. ß1-C dissociated into two electrophoretic components under a variety of conditions in addition to infections. Endotoxins and killed organisms in vivo, and specific precipitate absorption, heat and aging in vitro produced this change. Endotoxins injected into mice also induced a rise in haptoglobin though not as sharply or predictably as acute infection. Preliminary results with samples from hospital patients with acute diseases are discussed. It was concluded that study of experimental diseases in laboratory animals by these techniques could provide a fruitful basis for the investigation of the plasma protein changes in similar human diseases.

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

scholarly journals The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382199528
Author(s):  
Qing Lv ◽  
Qinghua Xia ◽  
Anshu Li ◽  
Zhiyong Wang
Keyword(s):  
Tumor Microenvironment ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Stomach Carcinoma ◽  
Downstream Target ◽  
Volume Weight

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

scholarly journals Unraveling the In Vivo Protein Corona

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 132
Author(s):  
Johanna Simon ◽  
Gabor Kuhn ◽  
Michael Fichter ◽  
Stephan Gehring ◽  
Katharina Landfester ◽  
...  
Keyword(s):  
Plasma Proteins ◽  
Ex Vivo ◽  
Protein Corona ◽  
Blood Proteins ◽  
Therapeutic Application ◽  
Complex Situation ◽  
Ex Vivo Approach ◽  
In Vivo Administration

Understanding the behavior of nanoparticles upon contact with a physiological environment is of urgent need in order to improve their properties for a successful therapeutic application. Most commonly, the interaction of nanoparticles with plasma proteins are studied under in vitro conditions. However, this has been shown to not reflect the complex situation after in vivo administration. Therefore, here we focused on the investigation of magnetic nanoparticles with blood proteins under in vivo conditions. Importantly, we observed a radically different proteome in vivo in comparison to the in vitro situation underlining the significance of in vivo protein corona studies. Next to this, we found that the in vivo corona profile does not significantly change over time. To mimic the in vivo situation, we established an approach, which we termed “ex vivo” as it uses whole blood freshly prepared from an animal. Overall, we present a comprehensive analysis focusing on the interaction between nanoparticles and blood proteins under in vivo conditions and how to mimic this situation with our ex vivo approach. This knowledge is needed to characterize the true biological identity of nanoparticles.

scholarly journals Neuroprotective Effect of Optimized Yinxieling Formula in 6-OHDA-Induced Chronic Model of Parkinson’s Disease through the Inflammation Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Renrong Wei ◽  
Cuiping Rong ◽  
Qingfeng Xie ◽  
Shouhai Wu ◽  
Yuchao Feng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Calcium Binding ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effect ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Cox 2

Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN)-striatum circuit, which is associated with glial activation and consequent chronic neuroinflammation. Optimized Yinxieling Formula (OYF) is a Chinese medicine that exerts therapeutical effect and antiinflammation property on psoriasis. Our previous study has proven that pretreatment with OYF could regulate glia-mediated inflammation in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Given that PD is a chronic degeneration disorder, this study applied another PD animal model induced by striatal injection of 6-hydroxydopamine (6-OHDA) to mimic the progressive damage of the SN-striatum dopamine system in rats. The OYF was administrated in the manner of pretreatment plus treatment. The effects of the OYF on motor behaviors were assessed with the apomorphine-induced rotation test and adjusting steps test. To confirm the effect of OYF on dopaminergic neurons and glia activation in this model, we analyzed the expression of tyrosine hydroxylase (TH) and glia markers, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP) in the SN region of the rat PD model. Inflammation-associated factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were further evaluated in this model and in interferon-γ- (INF-γ-) induced murine macrophages RAW264.7 cells. The results from the in vivo study showed that OYF reversed the motor behavioral dysfunction in 6-OHDA-induced PD rats, upregulated the TH expression, decreased the immunoreactivity of Iba-1 and GFAP, and downregulated the mRNA levels of TNF-α and COX-2. The OYF also trended to decrease the mRNA levels of IL-1β and iNOS in vivo. The results from the in vitro study showed that OYF significantly decreased the mRNA levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2. Therefore, this study suggests that OYF exerts antiinflammatory effects, which might be related to the protection of dopaminergic neurons in 6-OHDA-induced chronic neurotoxicity.

scholarly journals Role of Cathepsin S in Periodontal Inflammation and Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
S. Memmert ◽  
A. Damanaki ◽  
A. V. B. Nogueira ◽  
S. Eick ◽  
M. Nokhbehsaim ◽  
...  
Keyword(s):  
Periodontal Diseases ◽  
Interleukin 1 ◽  
Critical Role ◽  
Gingival Tissue ◽  
Cathepsin S ◽  
Protein Levels ◽  
Periodontal Inflammation

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.

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