scholarly journals Decreased expression levels of rat liver glutathione S-transferase A2 and albumin during the acute phase response are mediated by HNF1 (hepatic nuclear factor 1) and IL6DEX-NP

2004 ◽  
Vol 377 (3) ◽  
pp. 763-768 ◽  
Author(s):  
Richard WHALEN ◽  
Susan H. VOSS ◽  
Thomas D. BOYER
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Rat Hepatocytes ◽  
Phase Response ◽  
Negative Regulator ◽  
Nuclear Factor ◽  
Hepatic Nuclear Factor 1 ◽  
Nuclear Factor 1

The acute phase response is characterized by positive and negative regulation of many liver proteins including GSTs (glutathione S-transferases) and albumin. The expression of albumin and some GSTs are dependent on HNF1 (hepatic nuclear factor 1). Interleukin 6 plus dexamethasone induce a nuclear protein (IL6DEX-NP) in rat hepatocytes in vitro that binds to a promoter element adjacent to the HNF1 site of rGSTA2 and decreases its expression. We determined how HNF1 and IL6DEX-NP regulate rGSTA2 and albumin expression in rats during the acute phase response after LPS (lipopolysaccharide) treatment. Expression of rGSTA2 and albumin mRNA decreased 3 h after LPS treatment and remained low for 48 h. Transcription rates showed a similar pattern but albumin transcription was less affected. HNF1 and IL6DEX-NP binding to the rGSTA2 promoter was present in control livers but was absent at 3 and 6 h after LPS. By 12 h, HNF1 and IL6DEX-NP binding to the rGSTA2 promoter reappeared and increased to above normal at 48 h. The patterns of HNF1 and IL6DEX-NP binding to the albumin promoter were similar. Affinity of IL6DEX-NP for the albumin promoter was less than that for the rGSTA2 promoter and changes in the transcription rates were consistent with the difference. Early decreases in rGSTA2 and albumin during the acute phase response are due to decreased binding of HNF1. Later persistent decreases in transcriptional rate of rGSTA2 and to a lesser extent albumin are due to increased IL6DEX-NP binding. IL6DEX-NP appears to be an important negative regulator of gene expression in vitro and in vivo.

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.

scholarly journals Mechanism of negative regulation of rat glutathione S-transferase A2 by the cytokine interleukin 6

2002 ◽  
Vol 365 (1) ◽  
pp. 229-237 ◽  
Author(s):  
Susan H. VOSS ◽  
Richard WHALEN ◽  
Thomas D. BOYER
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Culture Media ◽  
Rat Hepatocytes ◽  
Phase Response ◽  
Negative Regulator ◽  
Glutathione S Transferase ◽  
Mobility Shift ◽  
Nuclear Factor 1

A decrease in concentration of some liver proteins, including the detoxification enzyme glutathione S-transferase A2 (rGSTA2), occurs during the acute-phase response. Interleukin 6 (IL-6) with dexamethasone (DEX) decreases transcription of rGSTA2 in rat hepatocytes. The promoter region that mediates suppression of rGSTA2 was localized to 150bp. These 150bp were divided and used for electrophoretic mobility-shift assays. Induction of a protein that specifically bound to an oligonucleotide from this region required new protein synthesis and IL-6 with DEX in the culture media. The protein bound to part of the hepatocyte nuclear factor 1 (HNF1) site but was different from and did not displace HNF1. A core sequence, TGATT, was required for binding. The protein also bound to an HNF1 site in the albumin promoter. We hypothesize that IL-6 along with DEX induced a novel protein that decreased transcription of rGSTA2 and possibly albumin by interfering with the transactivating function of HNF1. The protein may be an important negative regulator of transcription 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.

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.

In vitro release of ?1-acid glycoprotein RNA sequences shows fidelity with the acute phase response in vivo

1986 ◽  
Vol 11 (3) ◽  
pp. 163-172 ◽  
Author(s):  
G. A. Clawson ◽  
J. Button ◽  
C. H. Woo ◽  
Yu-Cheng Liao ◽  
E. A. Smuckler
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
In Vitro Release ◽  
Phase Response ◽  
Rna Sequences ◽  
Acid Glycoprotein ◽  
Vitro Release

Chylomicron-bound LPS inhibits activation of the acute phase response in vitro and in vivo

2003 ◽  
Vol 114 (2) ◽  
pp. 303
Author(s):  
J.S. Chang ◽  
D.H. Lee ◽  
A.E. Falor ◽  
F. Kasravi ◽  
H.W. Harris
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response

An In Vitro and In Vivo Study of Cytokines in the Acute-Phase Response Associated with Bisphosphonates

1997 ◽  
Vol 61 (5) ◽  
pp. 386-392 ◽  
Author(s):  
D. Thiébaud ◽  
A. Sauty ◽  
P. Burckhardt ◽  
P. Leuenberger ◽  
L. Sitzler ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response ◽  
In Vivo Study

Tissue-specific gene expression of prolactin receptor in the acute-phase response induced by lipopolysaccharides

2004 ◽  
Vol 287 (4) ◽  
pp. E750-E757 ◽  
Author(s):  
Ana M. Corbacho ◽  
Giuseppe Valacchi ◽  
Lukas Kubala ◽  
Estibaliz Olano-Martín ◽  
Bettina C. Schock ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Prolactin Receptor ◽  
Phase Response ◽  
Specific Gene ◽  
Mrna Levels ◽  
Tissue Specific ◽  
Specific Regulation

Acute inflammation can elicit a defense reaction known as the acute-phase response (APR) that is crucial for reestablishing homeostasis in the host. The role for prolactin (PRL) as an immunomodulatory factor maintaining homeostasis under conditions of stress has been proposed; however, its function during the APR remains unclear. Previously, it was shown that proinflammatory cytokines characteristic of the APR (TNF-α, IL-1β, and IFNγ) induced the expression of the PRL receptor (PRLR) by pulmonary fibroblasts in vitro. Here, we investigated the in vivo expression of PRLR during lipopolysaccharide (LPS)-induced APR in various tissues of the mouse. We show that PRLR mRNA and protein levels were downregulated in hepatic tissues after intraperitoneal LPS injection. Downregulation of PRLR in the liver was confirmed by immunohistochemistry. A suppressive effect on mRNA expression was also observed in prostate, seminal vesicle, kidney, heart, and lung tissues. However, PRLR mRNA levels were increased in the thymus, and no changes were observed in the spleen. The proportion of transcripts for the different receptor isoforms (long, S1, S2, and S3) in liver and thymus was not altered by LPS injection. These findings suggest a complex tissue-specific regulation of PRLR expression in the context of the APR.

scholarly journals Liver Receptor Homolog 1 Is a Negative Regulator of the Hepatic Acute-Phase Response

2006 ◽  
Vol 26 (18) ◽  
pp. 6799-6807 ◽  
Author(s):  
Nicolas Venteclef ◽  
Jason C. Smith ◽  
Bryan Goodwin ◽  
Philippe Delerive
Keyword(s):  
Inflammatory Response ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Ectopic Expression ◽  
Phase Response ◽  
Negative Regulator ◽  
Orphan Nuclear Receptor ◽  
Mobility Shift ◽  
Amyloid A

ABSTRACT The orphan nuclear receptor liver receptor homolog 1 (LRH-1) has been reported to play an important role in bile acid biosynthesis and reverse cholesterol transport. Here, we show that LRH-1 is a key player in the control of the hepatic acute-phase response. Ectopic expression of LRH-1 with adenovirus resulted in strong inhibition of both interleukin-6 (IL-6)- and IL-1β-stimulated haptoglobin, serum amyloid A, and fibrinogen β gene expression in hepatocytes. Furthermore, induction of the hepatic inflammatory response was significantly exacerbated in HepG2 cells expressing short hairpin RNA targeting LRH-1 expression. Moreover, transient-transfection experiments and electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that LRH-1 regulates this cytokine-elicited inflammatory response by, at least in part, antagonizing the CCAAT/enhancer binding protein β signaling pathway. Finally, we show, by using LRH-1 heterozygous mice, that LRH-1 is involved in the control of the inflammatory response at the hepatic level in vivo. Taken together, our results outline an unexpected role for LRH-1 in the modulation of the hepatic acute-phase response.

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