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 ◽  
...  

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.

1993 ◽  
Vol 11 (1) ◽  
pp. 31-36 ◽  
Author(s):  
P Hagan ◽  
S Poole ◽  
A F Bristow

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.


2004 ◽  
Vol 377 (3) ◽  
pp. 763-768 ◽  
Author(s):  
Richard WHALEN ◽  
Susan H. VOSS ◽  
Thomas D. BOYER

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.


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

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.


1986 ◽  
Vol 11 (3) ◽  
pp. 163-172 ◽  
Author(s):  
G. A. Clawson ◽  
J. Button ◽  
C. H. Woo ◽  
Yu-Cheng Liao ◽  
E. A. Smuckler

Cytokine ◽  
1995 ◽  
Vol 7 (6) ◽  
pp. 510-516 ◽  
Author(s):  
Hester S.A. Oldenburg ◽  
Hester S.A. Oldenburg ◽  
Jeffrey H. Pruitt ◽  
Douglas D. Lazarus ◽  
Douglas D. Lazarus ◽  
...  

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

1997 ◽  
Vol 61 (5) ◽  
pp. 386-392 ◽  
Author(s):  
D. Thiébaud ◽  
A. Sauty ◽  
P. Burckhardt ◽  
P. Leuenberger ◽  
L. Sitzler ◽  
...  

2004 ◽  
Vol 287 (4) ◽  
pp. E750-E757 ◽  
Author(s):  
Ana M. Corbacho ◽  
Giuseppe Valacchi ◽  
Lukas Kubala ◽  
Estibaliz Olano-Martín ◽  
Bettina C. Schock ◽  
...  

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.


1986 ◽  
Vol 103 (3) ◽  
pp. 787-793 ◽  
Author(s):  
G J Darlington ◽  
D R Wilson ◽  
L B Lachman

Human hepatoma cells mimic the acute phase response after treatment with monocyte-conditioned medium. Levels of secreted fibrinogen, alpha-1 acid glycoprotein, C-reactive protein, haptoglobin, and the third component of complement were elevated compared with control levels after 48 h of incubation with conditioned supernatant medium from an enriched fraction of normal peripheral monocytes. Albumin levels declined and alpha-1 antitrypsin remained unchanged. Levels of specific mRNA were measured by hybridization to slot blots and Northern blots and changed in correspondence with protein alterations. Interleukin-1 and tumor necrosis factor stimulated the third component of complement, but did not elevate any other member of the acute phase group and were therefore only partially active in this system. The identification of an in vitro model of the human acute phase response will permit analysis of the molecular basis for coordinate regulation of this group of facultative genes.


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