Biomedical subjects

J P Lebreton

Publications and source records attributed to J P Lebreton.

At least 19 recordsLinked to original sources

PubMed2001

Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock.

Oxidant-mediated reperfusion injury of the gut is a major contributor of the systemic inflammatory response in hemorrhagic shock. Recent studies have suggested that heme-oxygenase-1 (HO-1) represents an endogenous protective mechanism against oxidant stress. We assessed whether HO-1 induction modulates the synthesis of tumor necrosis factor-alpha (TNF-alpha) in hemorrhagic shock. In rats submitted to hemorrhagic shock, pretreatment with hemoglobin (Hb) increased HO-1 mRNA expression in macrophages. This increased expression was associated with a decreased expression of TNF-alpha mRNA, as well as decreased plasma concentrations of TNF-alpha. These effects of Hb were reduced by the HO-1 inhibitor tin-protoporphyrin (Sn-PP 20 micromol/kg), while Sn-PP had no effect in the absence of Hb. In parallel, Hb pretreatment reduced pulmonary edema, vascular injury, and increased mesenteric blood flow, and these effects were reduced by Sn-PP. Thus, induction of HO-1 is protective in hemorrhagic shock, possibly through its antioxidant properties. Interventions that induce HO-1 may be beneficial in the treatment of shock states, leading to a reduced systemic inflammatory response.

Animals↗

PubMed2001

Increase in cyclooxygenase-2 and nitric oxide-synthase-2 mRNAs in pouchitis without modification of inducible isoenzyme heme-oxygenase-1.

OBJECTIVES: The pathophysiology of pouchitis occurring after ileal pouch-anal anastomosis remains controversial. Prostaglandins and nitric oxide synthesized in excess by cyclooxygenase-2 and nitric oxide synthase-2 are thought to be involved in the inflammatory process. Because heme oxygenase-1, by its antioxidant properties, could modulate inflammatory reaction, we analyzed mRNAs of the three enzymes (cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-1) in patients with ileal pouch-anal anastomosis. METHODS: Endoscopic biopsies were obtained in eight patients with normal ileal pouch-anal anastomosis, in eight patients with pouchitis, and in normal ileum of six healthy subjects. A relative quantitative RT-PCR was performed to determine the levels of cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-1 mRNAs. RESULTS: Cyclooxygenase-2 and nitric oxide synthase-2 mRNAs were increased both in normal ileal pouch-anal anastomosis and in pouchitis, compared with healthy subjects. Pouchitis disease activity index was correlated with mRNA levels of cyclooxygenase-2 (r = 0.71; p < 0.01) and nitric oxide synthase-2 (r = 0.51; p < 0.05). Heme oxygenase-1 mRNA levels were not significantly different in patients versus healthy subjects. CONCLUSIONS: The increase in cyclooxygenase-2 and nitric oxide synthase-2 mRNA levels both in pouchitis and normal ileal pouch-anal anastomosis demonstrates that a latent inflammatory process occurs in the ileal pouch mucosa. This inflammatory process was not found to be associated with an induction of heme oxygenase mRNA, a possible regulator of the inflammatory response.

Adult↗

PubMed2000

[The platelet/leukocyte ratio in red blood cell concentrates is an essential indicator of leukocyte removal filter efficiency which limits their use].

Performances of filter systems for leucocyte removal (Pall BPF4 and Sepacell RZ 200 B) have been studied following the preparation of red blood cell concentrates (RBCCs) obtained either by a soft-spin centrifugation at 2967xg (n = 438) or by a hard-spin centrifugation at 5275xg (n = 187). After deleucocytation, 43, i.e., 9.8% of RBCCs obtained following a soft-spin centrifugation contained a number of residual leucocytes higher than 1 x 10(6) leucocytes/RBCC which represents the legal upper limit in France, whereas RBCCs obtained following a hard-spin centrifugation always contained a number of residual leucocytes lower than this limit. Our results strongly suggest that the quality of deleucocytation depends on an adequate ratio of platelets to leucocytes, which favours the capture of leucocytes by filters. In fact, this ratio was higher in RBCCs obtained following a hard-spin centrifugation. Our results demonstrate that the use of these filters does not allow the removal of leucocytes complying with the legal limit of leucodepletion for all preparations of RBCCs.

Cell Separation↗

PubMed2000

Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats.

OBJECTIVES: Intestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock. DESIGN: A prospective, controlled animal study. SETTING: A university research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Hemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr). MEASUREMENTS AND MAIN RESULTS: MPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85+/-6; MPG 35+/-5 mL/kg; p < .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-alpha (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-alpha and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-alpha and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation. CONCLUSION: Reactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.

Animals↗

PubMed1999

Protective effects of preconditioning in cultured rat endothelial cells: effects on neutrophil adhesion and expression of ICAM-1 after anoxia and reoxygenation.

BACKGROUND: Preconditioning with brief periods of ischemia protects the coronary endothelium against acute and chronic reperfusion injury, but the mechanisms of this endothelial protection remain unknown. We hypothesized that preconditioning protects endothelial cells through a decreased production of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), leading to a lesser adhesion of neutrophils to the endothelium. METHODS AND RESULTS: Cultured rat aortic endothelial cells were subjected to 6-hour anoxia followed by various durations of reoxygenation. Preconditioning was induced by 1-hour anoxia and 1-hour reoxygenation. ICAM-1 gene expression was measured by polymerase chain reaction, and the percentage of cells expressing ICAM-1 was assessed by confocal laser fluorescence microscopy. Anoxia/reoxygenation increased expression of ICAM-1, with a peak occurring after 6 hours of reoxygenation for mRNA and 9 hours for protein. Preconditioning prevented the increase in ICAM-1. Similar reductions were observed with the free radical scavenger N-2 mercaptopropionyl glycine (MPG). The inhibitory effect of preconditioning on ICAM-1 expression was abolished by an inhibitor of protein kinase C, an inhibitor of nitric oxide synthesis, and by MPG but was not affected by an adenosine receptor antagonist. Finally, both preconditioning and MPG partially prevented the increased adhesion of human neutrophils to reoxygenated endothelial cells. CONCLUSIONS: Preconditioning prevented reoxygenation-induced, free radical-mediated expression of ICAM-1 by a mechanism involving activation of protein kinase C and production of nitric oxide and free radicals, and this is associated with a lesser adhesion of neutrophils to endothelial cells. Such prevention of neutrophil adhesion may contribute to the protective effect of preconditioning against reperfusion-induced endothelial injury.

Animals↗

PubMed1999

Induction of haem oxygenase contributes to the synthesis of pro-inflammatory cytokines in re-oxygenated rat macrophages: role of cGMP.

Macrophage activation and the resulting inflammatory response may be a major component of tissue injury upon hypoxia and re-oxygenation. Activation of the haem oxygenase (HO)/carbon monoxide (CO) pathway may be an important regulator of the inflammatory response, through production of cyclic 3', 5'-monophosphate (cGMP). We have assessed whether HO contributes to the increased production of the pro-inflammatory cytokines TNF-alpha and IL-6 in re-oxygenated rat peritoneal macrophages.Hypoxia/re-oxygenation markedly increased levels of HO-1 mRNA and cGMP. The increase in cGMP was reduced by the HO-1 inhibitor tin-protoporphyrin (SnPP-9) given during re-oxygenation. Hypoxia and re-oxygenation also increased IL-6 and TNF-alpha mRNA expression, as well as IL-6 and TNF-alpha concentrations in the cell supernatant. These increases were nullified by SnPP-9 and by Methylene Blue, an inhibitor of guanylate cyclase, but were not affected by L-NNA, an inhibitor of NO synthesis. The inhibitory effect of SnPP on the synthesis of cytokines was reversed by co-administration of the stable analogue of cGMP, 8-Br-cGMP. Our results indicate that activation of haem oxygenase and of the CO/cGMP pathway is a major stimulus for the synthesis and release of pro-inflammatory cytokines in re-oxygenated macrophages. This pathway may play a central role in pathological situations in which local tissue hypoxia/re-oxygenation triggers a systemic inflammatory response, for example in patients with shock.

Animals↗

PubMed1999

Heme and acute inflammation role in vivo of heme in the hepatic expression of positive acute-phase reactants in rats.

Acute-phase protein synthesis in the liver during inflammation is regulated via cytokines and glucocorticoids. Using quantitative reverse transcription (RT)-PCR analysis and immunoassay, we explored, in the rat, the response of the acute-phase protein, alpha-2 macroglobulin (A2M), after systemic inflammation induced by lipopolysaccharide (LPS) or localized inflammation induced by turpentine oil (TO). The results indicate that synthesis of A2M is higher following TO-induced inflammation than LPS-induced inflammation and is not correlated with interleukin (IL)-6 or glucocorticoid levels. We studied the putative role of heme in this differential A2M expression following localized vs. systemic inflammation; addition of heme during LPS-induced inflammation can boost the expression of A2M, whereas blocking heme synthesis (by succinyl acetone) or enhancing its consumption in parallel biosynthetic pathways (cytochrome P450 induction by phenobarbital) decreases A2M expression. This decrease was abolished by exogenous heme supplementation. Finally, we demonstrate that heme supplementation is also able to increase the A2M response in female rats to a level similar to that in male rats providing a new insight into the puzzling sexual dimorphism observed previously during localized inflammation. We propose that heme should be considered a new regulatory element in controlling liver A2M expression during inflammation.

Acute-Phase Proteins↗

PubMed1999

Differential regenerative response and expression of growth factors following hepatectomy of variable extent in rats.

AIMS/BACKGROUND: Liver regeneration is a physiological mechanism which leads to restoration of the hepatic parenchyma following hepatectomy or toxic injury. This process is mediated by a wide variety of cytokines and growth factors. The aim of the present study was to evaluate the influence of hepatectomy extent on the levels of intrahepatic mRNAs for cell-cycle markers and growth factors in rats submitted to a 30%, two-third or 80% hepatectomy. METHODS: Cyclins, thymidine kinase and growth factors mRNA levels were quantitatively assessed by RT-PCR at different time points post-hepatectomy (2h, 6h, 12h, days 1, 2, 6). RESULTS: As compared with a two-third hepatectomy, cyclins and thymidine kinase mRNA levels were increased but with a delayed peak at day 2 in the 80% hepatectomy group and showed a progressive increase until day 6 in the 30% hepatectomy group; mRNA levels for HGF or TGFalpha were increased with a delayed peak at 12 h or day 2 in the 80% hepatectomy group, respectively and this delay was more pronounced in the 30% hepatectomy group with a peak at day 1 or day 6. CONCLUSION: A regenerative response occurs whatever the extent of hepatectomy but the course of regeneration and expression of growth factors differs according to the volume of resected liver. A better knowledge of these events could improve the clinical results of hepatic resection for primary or metastatic liver disease.

Animals↗

PubMed1998

Structural and functional analysis of the 5'-transcription control region for the human alpha2-HS glycoprotein gene.

The human alpha2-HS glycoprotein (A2HS) and rat phosphoprotein of Mr 63000 (pp63) are homologous plasma proteins and members of the fetuin superfamily. A2HS is involved in important functions such as inhibition of the tyrosine kinase activity of the insulin receptor, regulation of calcium metabolism and osteogenesis as well as protease inhibitory activity. We report an analysis of the 5' transcription control region (4 kb) of the A2HS gene. Its most proximal 300 nt display a very potent transcriptional activity. The latter is likely accounted for by C/EBP and NF1 binding sites that are conserved from the human A2HS gene to the rat pp63 gene. In contrast, these human and rat genes appear to largely diverge beyond their proximal promoter.

Base Sequence↗

PubMed1998

Hepatic and extra-hepatic transcription of inter-alpha-inhibitor family genes under normal or acute inflammatory conditions in rat.

The expression and level of the mRNAs for the five genes that code for a set of plasma proteins collectively referred to as the inter-alpha-inhibitor family have been studied in rat under a normal condition or in the course of a turpentine-induced, systemic inflammation. In healthy rats, all five mRNAs [H1, H2, H3, H4, and alpha1-microglobulin/bikunin precursor (AMBP)] are expressed primarily in liver and two of them (H2 and H3) are found to a lower extent in brain. By in situ hybridization onto sections of a normal brain, the H3 mRNA has been precisely localized to the hypothalamus, amygdala, pontine area, optic tectum, and cerebellum. By reverse transcriptase-polymerase chain reaction of total RNAs obtained from a panel of organs, low amounts of one or more mRNA(s) could be detected in other locations (e.g., intestine and stomach). Furthermore, the extrahepatic expressions of several of these genes are up- or downregulated at 20 h after the start of a turpentine-induced inflammation. In liver, the contents of H3 and H4 mRNA are upregulated, whereas those of AMBP and H2 are downregulated during the acute phase. This is accounted for by changes in gene transcription, the kinetics of which is gene-specific. This behavior of H1, H2, H3, H4, and AMBP mRNAs in rat liver is in keeping with more limited analyses made at mRNA and/or protein levels in other species (human, pig) suffering from an acute inflammation. Therefore, the inflammation-associated regulation of these five genes that is conserved between species indicates that the inter-alpha-inhibitor family members are likely to be important partners of the acute phase response.

Alpha-Globulins↗

PubMed1998

Human recombinant alpha 2-HS glycoprotein is produced in insect cells as a full length inhibitor of the insulin receptor tyrosine kinase.

Human Alpha 2-HS glycoprotein (AHSG), a glycoprotein synthesized by hepatocytes, was expressed in insect cells using the recombinant baculovirus system. The protein was purified from the cell supernatant, and appeared as a single band at about 52 kDa. Western blot using a specific antibody to the B-chain of AHSG indicated that the connecting peptide was present in the protein. When incubated with solubilized insulin receptors, recombinant AHSG inhibited the tyrosine kinase activity of the receptors in a dose-dependent fashion at concentrations in the range of those of the circulating protein. AHSG did not interfere with the binding of insulin to its receptor. These results indicate that human AHSG represents a natural inhibitor of the insulin receptor tyrosine kinase, is active as a single-chain protein and possesses a biological role similar to that of its homologue in rats, pp63, described by Auberger et al. (1).

Baculoviridae↗

PubMed1998

Induction and modulation of acute-phase response by protein malnutrition in rats: comparative effect of systemic and localized inflammation on interleukin-6 and acute-phase protein synthesis.

The acute-phase protein (APP) response is regulated by cytokines such as interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor (TNF), but may also be influenced by malnutrition. The aims of this study were as follows: 1) to determine in rats the effect of a protein-deficient diet on IL-6 mRNA expression in intestine, liver and peripheral blood mononuclear cells (PBMC), and on alpha-1 acid glycoprotein (AGP) and alpha-2 macroglobulin (A2M) serum levels and hepatic mRNA expression; 2) to compare, in protein-deficient rats, the IL-6 and APP responses after a turpentine (TO)- or a lipopolysaccharide (LPS)-induced inflammation; and 3) to determine the effect of a protein malnutrition on IL-6 mRNA expression in rat PBMC treated ex vivo with LPS. Interleukin-6 mRNA was present in intestine and PBMC but not in the liver of malnourished rats, and was absent in any tissue or cells of controls. A2M was present in the serum from malnourished rats but not after refeeding. AGP mRNA expression was not influenced by protein malnutrition. In malnourished rats, IL-6 serum level peaked later than in controls after TO and LPS treatment. In malnourished TO-treated rats, A2M mRNA increased earlier than in controls and remained detectable later than in controls. AGP mRNA expression after TO was not influenced by protein malnutrition. In PBMC of malnourished rats, LPS-induced IL-6 mRNA expression occurred earlier and lasted longer than in controls. Our results indicate that protein malnutrition by itself induces IL-6 and A2M expression, and that it modulates the APP response to inflammation.

Acute-Phase Proteins↗

PubMed1998

Nitric oxide synthase inhibition and the induction of cytochrome P-450 affect heme oxygenase-1 messenger RNA expression after partial hepatectomy and acute inflammation in rats.

OBJECTIVES: a) To evaluate in vivo, in rat liver, heme oxygenase-1 (HO-1) messenger RNA (mRNA) expression level and the regulation of 3',5'-cyclic guanosine monophosphate (cGMP) production during hepatic regeneration, localized inflammation, and systemic inflammation; and b) to investigate the effect of the induction of cytochrome P-450 and nitric oxide synthase (NOS) inhibition on HO-1 mRNA level and cGMP production in the liver. DESIGN: Experimental, comparative study. SETTING: Biochemical and molecular biology laboratory. SUBJECTS: Six-wk-old male Sprague-Dawley rats (n = 60). INTERVENTIONS: We randomly divided the rats into four groups: a) saline controls; b) animals receiving lipopolysaccharide (600 microg/kg) for systemic inflammation; c) animals receiving turpentine oil (5 mL/kg) for localized inflammation obtained by sterile abscess; and d) partially hepatectomized animals (two-thirds removal of the parenchyma) for hepatic regeneration. MEASUREMENTS AND MAIN RESULTS: Hepatic regeneration induced HO-1 mRNA expression, as shown by quantitative reverse transcription-polymerase chain reaction analysis. The time course of liver HO-1 mRNA induction after partial hepatectomy and localized and systemic inflammation showed a similar and gradual increase, with a maximum at 6 hrs and a return to a minimal level 48 hrs after treatments. Liver HO-1 mRNA was overexpressed during localized vs. systemic inflammation. This overexpression was not correlated with either serum IL-6 or corticosterone concentrations, but is related to increased cGMP production. The administration of phenobarbital, a cytochrome P-450 inducer and of nitro-L-arginine methyl ester, a NOS inhibitor, prevented cGMP production and abolished the overexpression of HO-1 mRNA. CONCLUSIONS: The results of this study indicate that HO-1 mRNA is induced during hepatic regeneration with a similar time course to that observed during acute inflammation. In addition, we demonstrated that: a) HO-1 mRNA is overexpressed during localized vs. systemic inflammation; b) this overexpression is not correlated with IL-6 or corticosterone concentrations but is related to intrahepatic cGMP production; c) induction of cytochromes P-450 and/or inhibition of NOS both reduce liver cGMP production and HO-1 mRNA expression. These results suggest that in rat liver, a cGMP-transducing pathway may control HO-1 mRNA expression. Thus, there may be a role for HO-1 mRNA in the modulation of the hepatic stress response.

Acute Disease↗

PubMed1997

Cytokine gene expression in liver following minor or major hepatectomy in rat.

Interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and transforming growth factors alpha and beta (TGF-alpha and TGF-beta) are important mediators which play a pleiotropic role in both inflammatory and hepatic regeneration processes. It has also been proposed that a major hepatectomy impairs the liver-related host defence mechanisms. The aim of this study was to evaluate the influence of minor (30%) vs major (80%) hepatectomy on cytokines, growth factors and acute-phase proteins both at the protein and mRNA levels in rat. For that purpose, rats were submitted to either 30% or 80% hepatectomy and sacrificed at intervals up to day 14 post-hepatectomy to collect liver and blood samples. Serum levels of IL-6 and acute-phase proteins (APPs) were determined after RNA extraction, cytokine and acute-phase proteins gene expression were evaluated using a quantitative RT-PCR method. The results demonstrate that liver mRNA levels for IL-6 were early unregulated after a 80% resection only, whereas liver mRNA levels for IL-1 slowly increased following 30 or 80% hepatectomy. For TNF-alpha, no significant changes were observed between groups. Growth factor expression differed according to the extent of hepatic resection. Moreover, plasma levels of alpha2-macroglobulin (alpha2M) and alpha1 acid glycoprotein (AGP), two major APPs which respond differently to combination of cytokines, were significantly lowered after a major resection whereas levels of serum IL-6 showed no significant changes between groups. Paradoxically, in the 80% hepatectomized group, alpha2M mRNA expression was strongly increased at 4 h and 6 h post-hepatectomy as compared with the 30% hepatectomized group. Taken together, these results suggest that, although an increased level of hepatic IL-6 expression was observed following a major resection, the liver's capacity to synthesize normal levels of APPs was impaired. Moreover, these specific changes of cytokine gene expression seen in the liver following major hepatectomy might reflect a preferential activation of the IL-6-dependent APPs.

Acute-Phase Proteins↗

PubMed1997

Transforming growth factor alpha (TGF-alpha) expression correlates with DNA replication in regenerating rat liver whatever the hepatectomy extent.

Liver regeneration is a physiological mechanism that leads to restoration of the hepatic parenchyma following hepatectomy or toxic injury. As a two-third hepatectomy is the usual model to analyse this phenomenon, few studies have compared liver regeneration after minor vs major hepatectomy. We have used a quantitative RT-PCR technique to study the hepatic transcription of the TGF-alpha gene in rats submitted to 30% or 80% hepatectomy and we have correlated this transcription with the regenerative response assessed by flow cytometry and Ki-67 expression. The level of TGF-alpha expression and the regenerative response were different, according to the volume of liver removed, and were statistically correlated (r = 0.679, p = 0.002). TGF-alpha expression and phase S peaked at day 2 vs 6 in the 80% vs 30% hepatectomized rat groups, respectively. Ki-67 expression occurred at 2 h post-hepatectomy in the two groups of rats and was observed until day 14 mainly in the 80% hepatectomy group. Our results indicate that TGF-alpha expression in regenerating liver is strongly correlated with hepatocyte mitosis, that a delayed regenerative response occurs following 30% hepatectomy and that the course of regeneration differs between minor vs major hepatectomy.

Animals↗

PubMed1997

Gut ischemia and mesenteric synthesis of inflammatory cytokines after hemorrhagic or endotoxic shock.

The intestine plays a major role in the pathophysiology of multiorgan failure. Although the systemic inflammatory response might be induced by endotoxin released through bacterial translocation, other factors such as intestinal ischemia might be implicated. We investigated the relationship between intestinal ischemia-reperfusion and cytokine release in rat models of hemorrhagic or endotoxic shock. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), lactate, and endotoxin, as well as macrophage TNF-alpha and IL-6 mRNA expression, were assessed at the end of shock and resuscitation. Hemodynamic changes and lactate levels suggested the presence of intestinal ischemia in both models. Mesenteric levels of TNF-alpha and IL-6 were increased by hemorrhage and further increased after saline resuscitation. Similar results were obtained with mRNA cytokine gene expression in macrophages. Endotoxin was not detectable in the hemorrhagic group. Endotoxic shock also increased production of cytokines, which, in contrast to hemorrhage, was not further increased by resuscitation. These results suggest that intestinal ischemia-reperfusion upon hemorrhage and resuscitation may be a major trigger for cytokine gene expression in the absence of endotoxin.

Animals↗

PubMed1997

Titan and the origin of life on Earth.

The relevance of Titan to the study of pre-biotic chemistry and the origin of life on Earth will be addressed by an interdisciplinary group of Cassini/Huygens scientists using the different, but synergistic data sets obtained by NASA's Cassini Orbiter and ESA's Huygens Probe. Titan's special importance lies in the primitive chemically-reducing nature of its atmosphere Cassini/ Huygens instruments will determine what compounds form in this environment, and the results will be compared with models for pre-biological chemical evolution on Earth.

Atmosphere↗

PubMed1996

Differential expression of cytokine genes in monocytes, peritoneal macrophages and liver following endotoxin- or turpentine-induced inflammation in rat.

Pro-inflammatory cytokines are produced after systemic or local inflammation by a wide variety of cell types including monocytes, macrophages, Kupffer and endothelial cells. Previous studies have shown that IL-6 gene expression does not occur in liver from rats undergoing an acute phase response after turpentine injection or controls. These data do not rule out the possibility that delivery of a pathogen to the liver via the portal circulation could directly activate the Kupffer cells. Rats were injected either intravenously or intraperitoneally with LPS, or subcutaneously with turpentine oil. The changes in IL-1 beta, IL-6, and TNF mRNA levels in monocytes (collected from portal vein or caval cein), peritoneal macrophages and liver over a 3-hour period post-treatment were examined. The kinetics of LPS-vs turpentine-induced cytokine mRNAs in these various cell types were compared by quantitative reverse transcription and polymerase chain reaction (RT-PCR). Our data demonstrate that an intrahepatic expression of cytokines in the non parenchymal cells was induced by an LPS challenge but not by a turpentine-induced inflammation. This process could act as a paracrine mechanism in the acute-phase response and play a role in the modulation of hepatic regeneration.

Animals↗