scholarly journals Effects of human recombinant interleukin-1β on protein synthesis in rat tissues compared with a classical acute-phase reaction induced by turpentine. Rapid response of muscle to interleukin-1β

1991 ◽  
Vol 279 (3) ◽  
pp. 683-688 ◽  
Author(s):  
P E Ballmer ◽  
M A McNurlan ◽  
B G Southorn ◽  
I Grant ◽  
P J Garlick

The early time course (1, 3, 9, 24 h) of changes in rates of protein synthesis (ks) in liver and three different muscles (gastrocnemius, soleus and heart) was investigated after injection of saline, interleukin-1 beta (IL-1) or turpentine in rats. IL-1 injection induced a consistent increase in body temperature of about 3 degrees C between 3 and 5 h, but thereafter a hypothermic response occurred. With turpentine, a delayed fever response with a peak value by 9 h was observed. Both IL-1 and turpentine had no effect on protein synthesis in the small intestine, but produced a significant increase in ks in the liver at 9 h. By 24 h in IL-1-treated animals, liver ks had returned back to control values, whereas the turpentine-treated group showed a progressive rise in ks. Gastrocnemius and soleus muscles exhibited a significant fall in ks at 9 h after IL-1 and turpentine injection compared with the control. In contrast, the ks of heart muscle increased at 3-9 h after IL-1 injection, but there was no effect of turpentine. Thus for the first time a marked decrease of protein synthesis in skeletal muscle in response to IL-1 could be demonstrated.

1993 ◽  
Vol 85 (3) ◽  
pp. 337-342 ◽  
Author(s):  
Peter E. Ballmer ◽  
Margaret A. McNurlan ◽  
Ian Grant ◽  
Peter J. Garlick

1. The influence of an acute-phase reaction on the ability of protein synthesis rates in liver and three different muscles (gastrocnemius, soleus and heart) to respond to a short intravenous infusion of nutrients (glucose plus amino acids) was investigated during experimental inflammation induced by injection of human recombinant interleukin-1β or turpentine in young male rats. 2. Interleukin-1β induced a consistent increase of 3°C in body temperature between 3 and 5 h after injection, whereas turpentine induced a delayed fever, peaking by 13 h. 3. Interleukin-1β and turpentine stimulated fractional rates of protein synthesis in liver. The synthesis rate was inhibited by interleukin-1β in gastrocnemius and soleus muscle, but an elevation was seen in heart muscle. In this study there was no significant response of muscle to turpentine injection. 4. Two hours of parenteral nutrition increased fractional synthesis rates in all tissues when compared with Ringer's lactate. Somewhat larger responses to feeding were observed as a result of either interleukin-1β or turpentine injection in all tissues, but these improvements were not significant. 5. We conclude that the response of protein synthesis rates in liver and skeletal muscle to parenteral nutrition is not inhibited, and may be somewhat enhanced, during acute inflammatory conditions in the growing rat.


1996 ◽  
Vol 135 (5) ◽  
pp. 1341-1354 ◽  
Author(s):  
M Deshmukh ◽  
J Vasilakos ◽  
T L Deckwerth ◽  
P A Lampe ◽  
B D Shivers ◽  
...  

Sympathetic neurons undergo programmed cell death (PCD) when deprived of NGF. We used an inhibitor to examine the function of interleukin-1 beta-converting enzyme (ICE) family proteases during sympathetic neuronal death and to assess the metabolic and genetic status of neurons saved by such inhibition. Bocaspartyl(OMe)-fluoromethylketone (BAF), a cell-permeable inhibitor of the ICE family of cysteine proteases, inhibited ICE and CPP32 (IC50 approximately 4 microM) in vitro and blocked Fas-mediated apoptosis in thymocytes (EC50 approximately 10 microM). At similar concentrations, BAF also blocked the NGF deprivation-induced death of rat sympathetic neurons in culture. Compared to NGF-maintained neurons, BAF-saved neurons had markedly smaller somas and maintained only basal levels of protein synthesis; readdition of NGF restored growth and metabolism. Although BAF blocked apoptosis in sympathetic neurons, it did not prevent the fall in protein synthesis or the increase in the expression of c-jun, c-fos, and other mRNAs that occur during neuronal PCD, implying that the ICE-family proteases function downstream of these events during PCD.NGF and BAF rescued sympathetic neurons with an identical time course, suggesting that NGF, in addition to inhibiting metabolic and genetic events associated with neuronal PCD, can act posttranslationally to abort apoptosis at a time point indistinguishable from the activation of cysteine proteases. Both poly-(ADP ribose) polymerase and pro-ICE and Ced-3 homolog-1 (ICH-1) appear to be cleaved in a BAF-inhibitable manner, although the majority of pro-CPP32 appears unchanged, suggesting that ICH-1 is activated during neuronal PCD. Potential implications of these findings for anti-apoptotic therapies are discussed.


2002 ◽  
Vol 282 (5) ◽  
pp. E1029-E1038 ◽  
Author(s):  
Giuseppe Caso ◽  
G. Charles Ford ◽  
K. Sreekumaran Nair ◽  
Peter J. Garlick ◽  
Margaret A. McNurlan

Muscle protein synthesis in dogs measured by flooding withl-[2H5]phenylalanine (70 mg/kg) was significantly stimulated by infusion of insulin with amino acids. The stimulation of muscle protein synthesis was similar when calculated from the enrichment of phenylalanyl-tRNA (61 ± 10%, P< 0.001), plasma phenylalanine (61 ± 10%, P < 0.001), or tissue fluid phenylalanine (54 ± 10%, P < 0.001). The time course for changes in enrichment ofl-[2H5]phenylalanine throughout the flooding period was determined for plasma, tissue fluid, and phenylalanyl-tRNA in the basal state and during the infusion of insulin with amino acids. Enrichments of plasma free phenylalanine and phenylalanyl-tRNA were equalized between 20 and 45 min, although the enrichment of phenylalanyl-tRNA was lower at early time points. Rates of muscle protein synthesis obtained with the flooding method and calculated from plasma phenylalanine enrichment were comparable to those calculated from phenylalanyl-tRNA and also to those obtained previously with a continuous infusion of phenylalanine with phenylalanyl-tRNA as precursor. This study confirms that, with a bolus injection of labeled phenylalanine, the enrichment of aminoacyl-tRNA, the true precursor pool for protein synthesis, can be assessed from more readily sampled plasma phenylalanine.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2894
Author(s):  
Christian R. Pangilinan ◽  
Li-Hsien Wu ◽  
Che-Hsin Lee

Targeting metastasis is a vital strategy to improve the clinical outcome of cancer patients, specifically in cases with high-grade malignancies. Here, we employed a Salmonella-based treatment to address metastasis. The potential of Salmonella as an anticancer agent has been extensively studied; however, the mechanism through which it affects metastasis remains unclear. This study found that the epithelial-to-mesenchymal transition (EMT) inducer SNAI1 was markedly reduced in Salmonella-treated melanoma cells, as revealed by immunoblotting. Furthermore, wound healing and transwell assays showed a reduced in vitro cell migration following Salmonella treatment. Transfection experiments confirmed that Salmonella acted against metastasis by suppressing protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling, which in turn inhibited SNAI1 expression. Since it is known that metastasis is also influenced by inflammation, we partly characterized the immune infiltrates in melanoma as affected by Salmonella treatment. We found through tumor-macrophage co-culture that Salmonella treatment increased high mobility group box 1 (HMGB1) secretion in tumors to coax the polarization of macrophages in favor of an M1-like phenotype, as shown by increased inducible nitric oxide synthase (iNOS) expression and Interleukin 1 Beta (IL-1β) secretion. Data from our animal study corroborated the in vitro findings, wherein the Salmonella-treated group obtained the lowest lung metastases, longer survival, and increased iNOS-expressing immune infiltrates.


1994 ◽  
Vol 13 (1) ◽  
pp. 54-55
Author(s):  
O.E. Rooyackers ◽  
A.J.M. Wagenmakers ◽  
G. Hornstra

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