Early response to bleomycin is characterized by different cytokine and cytokine receptor profiles in lungs

2004 ◽  
Vol 287 (6) ◽  
pp. L1186-L1192 ◽  
Author(s):  
Eleonora Cavarra ◽  
Fabio Carraro ◽  
Silvia Fineschi ◽  
Antonella Naldini ◽  
Barbara Bartalesi ◽  
...  
Keyword(s):  
Rnase Protection Assay ◽  
Early Response ◽  
Receptor Expression ◽  
Cytokine Receptor ◽  
Cytokine Receptors ◽  
Mouse Strains ◽  
Ether Anesthesia ◽  
Rnase Protection ◽  
Tnf Α ◽  
Different Strains

The sensitivity to the fibrosis-inducing effect of bleomycin varies considerably from species to species, the reasons for which are unknown. The variability of the response in different strains of mice is well documented. Recent evidence indicates that the upregulated expression of cytokines and cytokine receptors may be involved. We evaluated the expression pattern of some cytokines and their receptors in C57Bl/6J bleomycin-sensitive and Balb/C bleomycin-resistant mice. Animals from both strains received, under ether anesthesia, either saline (50 μl) or bleomycin (0.1 U/50 μl) intratracheally. At various times after the treatment, the lungs were analyzed for cytokines and cytokine receptors by histochemistry and their mRNA by RNase protection assay. A significantly increased expression of TNF-α and IL-1β was observed in both strains. However, an upregulated lung expression for TNF-α and IL-1 receptors was observed in C57Bl/6J-sensitive animals only. This profile is evident from 63 h onward. In addition to TNF-α, bleomycin administration also resulted in the upregulated expression of TGF-β in the lungs of both strains at 8 h and in an enhanced expression of TGF-β receptors I and II in C57Bl/6J mice only. The upregulation of TGF-β receptor expression was preceded in this strain by an increased expression of IL-4, IL-13, and IL-13 receptor-α (at 8 h after bleomycin) and followed by an upregulation of gp130 and IL-6. The difference we observed in the cytokine receptor profile may offer an additional explanation for the different fibrogenic response of the two mouse strains to bleomycin.

Cytokines and endotoxin induce cytokine receptors in skeletal muscle

2000 ◽  
Vol 279 (1) ◽  
pp. E196-E205 ◽  
Author(s):  
Yan Zhang ◽  
Geneviève Pilon ◽  
André Marette ◽  
Vickie E. Baracos
Keyword(s):  
Skeletal Muscle ◽  
Interleukin 1 ◽  
Intraperitoneal Administration ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Cytokine Receptor ◽  
Cytokine Receptors ◽  
Type I ◽  
Skeletal Muscle Function ◽  
Tnf Α

Proinflammatory cytokines are important factors in the regulation of diverse aspects of skeletal muscle function; however, the muscle cytokine receptors mediating these functions are uncharacterized. Binding kinetics (dissociation constant = 39 ± 4.7 × 10−9M, maximal binding = 3.5 ± 0.23 × 10−12mol/mg membrane protein) of muscle tumor necrosis factor (TNF) receptors were obtained. Skeletal muscle was found to express mRNAs encoding interleukin-1 type I and II receptors, interleukin-6 receptor (IL-6R), and interferon-γ receptor by RT-PCR, but these receptors were below limits of detection of ligand-binding assay (≥1 fmol binding sites/mg protein). Twenty-four hours after intraperitoneal administration of endotoxin to rats, TNF receptor type II (TNFRII) and IL-6R mRNA were increased in skeletal muscle ( P < 0.05). In cultured L6 cells, the expression of mRNA encoding TNFRII and IL-6R receptors was induced by TNF-α, and all six cytokine receptor mRNA were induced by a mixture of TNF-α, IFN-γ, and endotoxin ( P < 0.05). This suggests that the low level of cytokine receptor expression is complemented by a capacity for receptor induction, providing a clear mechanism for amplification of cytokine responses at the muscle level.

scholarly journals Cytokine regulation of glutamate decarboxylase biosynthesis in isolated rat islets of Langerhans

1996 ◽  
Vol 317 (3) ◽  
pp. 713-719 ◽  
Author(s):  
Robert S. SCHMIDLI ◽  
Beverly E. FAULKNER-JONES ◽  
Leonard C. HARRISON ◽  
Roger F. L. JAMES ◽  
Henry J. DeAIZPURUA
Keyword(s):  
Protein Synthesis ◽  
Glutamate Decarboxylase ◽  
Rnase Protection Assay ◽  
Rabbit Antiserum ◽  
Β Cell ◽  
Rnase Protection ◽  
Rat Islets ◽  
Cell Destruction ◽  
Tnf Α ◽  
Ifn Γ

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which cytokines are thought to play an important role in β-cell destruction and immune regulation. A major target of β-cell autoimmunity in IDDM is the enzyme glutamate decarboxylase (GAD). We hypothesized that cytokines in the insulitis lesion modulate the synthesis of GAD. This may, in turn, modify the rate of β-cell destruction. Accordingly we cultured rat islets in the presence and absence of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum that recognizes both GAD65 and GAD67. Incubation of islets with interleukin (IL)-1β (1 ng/ml, 24 h), tumour necrosis factor α (TNF-α; 200 units/ml, 24 h) or interferon γ (IFN-γ; 500 units/ml, 72 h) significantly decreased the synthesis of both GAD65 and GAD67, but reduced neither total protein synthesis nor insulin accumulation in the medium or content. Incubation of islets for 24 h in IFN-α (1000 units/ml), TNF-β (50 ng/ml), IL 2 (1000 units/ml), IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or transforming growth factor β2 (TGF-β2; 5 ng/ml) did not significantly alter GAD65 or GAD67 synthesis. Inhibition of GAD65 and GAD67 protein synthesis by IL-1β, TNF-α or IFN-γ was reversed by co-incubation with the nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). Expression of both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased by IL-1β and completely restored to baseline levels by NMMA. Thus the synthesis of both isoforms of islet GAD is selectively decreased in the presence of IL-1β, TNF-α or IFN-γ by a NO-mediated mechanism, probably at the level of cytokine gene transcription. As GAD autoimmunity has been previously shown to have a pathogenic role in an animal model of IDDM, its inhibition by cytokines might limit the immune response, thereby regulating the rate of β-cell destruction in IDDM.

Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-α

1998 ◽  
Vol 275 (6) ◽  
pp. L1110-L1119 ◽  
Author(s):  
Edward G. Barrett ◽  
Carl Johnston ◽  
Günter Oberdörster ◽  
Jacob N. Finkelstein
Keyword(s):  
Epithelial Cells ◽  
Cell Line ◽  
Rnase Protection Assay ◽  
Alveolar Type ◽  
Mrna Levels ◽  
Type Ii ◽  
Rnase Protection ◽  
Tnf Α ◽  
Type Ii Cell ◽  
Ifn Γ

Recent evidence has suggested that epithelial cells may contribute to the inflammatory response in the lung after exposure to crystalline silica through the production of and response to specific growth factors, chemokines, and cytokines. However, the exact cellular and molecular responses of epithelial cells to silica exposure remains unclear. Using a murine alveolar type II cell line [murine lung epithelial (MLE)-15 cell line], we measured the early changes in various cytokine and chemokine mRNA species after exposure of the cells to 4–35 μg/cm2 of silica (cristobalite), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) alone or in combination. Total mRNA was isolated and assayed with an RNase protection assay after 6 and 24 h of exposure. Cristobalite exposure alone led to an increase in monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-2, and regulated on activation normal T cells expressed and secreted (RANTES) mRNAs. Treatment with IFN-γ alone increased MCP-1 mRNA levels. Treatment with TNF-α or LPS alone led to an increase in MCP-1 and MIP-2 mRNA. The combination of cristobalite plus TNF-α led to an additive increase in MCP-1 and MIP-2, whereas cristobalite plus IFN-γ or LPS had a synergistic effect. We also found with a TNF-α-neutralizing antibody that TNF-α plays a major role in mediating the type II cell chemokine response to cristobalite exposure. The results indicate that the cristobalite-induced chemokine response in the lung epithelium is mediated in part by TNF-α and can be enhanced by macrophage- and lymphocyte-derived inflammatory mediators in an additive and synergistic fashion.

scholarly journals Maternal immune activation causes age-specific changes in cytokine receptor expression in offspring throughout development

2018 ◽  
Author(s):  
Myka L. Estes ◽  
Bradford M. Elmer ◽  
Cameron C. Carter ◽  
A. Kimberley McAllister
Keyword(s):  
Immune Activation ◽  
Synapse Formation ◽  
Early Adulthood ◽  
Neuropsychiatric Disorders ◽  
Receptor Expression ◽  
Cytokine Receptor ◽  
Cytokine Receptors ◽  
Cytokine Signaling ◽  
Peak Period ◽  
Maternal Immune Activation

Maternal infection is a shared environmental risk factor for a spectrum of neuropsychiatric disorders and animal models of maternal immune activation (MIA) exhibit a range of neuropathologies and behaviors with relevance to these disorders. In particular, MIA offspring show chronic, age- and region-dependent changes in brain cytokines, a feature seen in postmortem studies of individuals with neuropsychiatric disorders. These MIA-induced alterations in brain cytokines may index biological processes underlying progression to diagnosable neuropsychiatric disorders. However, cytokines signal through specific cytokine receptors to alter cellular processes and it is the levels of those receptors that are critical for signaling. Yet, it remains unknown whether MIA alters the expression of cytokine receptors in the brains of offspring throughout postnatal development. Here, we measured the expression of 23 cytokine receptors in the frontal cortex of MIA and control offspring from birth to adulthood using qPCR. MIA offspring show dynamic oscillating alterations in cytokine receptors during sensitive periods of neural growth and synaptogenesis. Of the many cytokine receptors altered in the FC of MIA offspring, five were significantly changed at multiple ages at levels over 2-fold relative to controls (Il1r1, Ifngr1, Il10ra, Cx3cr1 and Gmcsfr), suggesting persistent dysfunction within those pathways. In addition to facilitating immune responses, these cytokine receptors play critical roles in neuronal migration and maturation, synapse formation and elimination, and microglial function. Together with previously reported changes in cytokine levels in the brains of MIA offspring, our results show a decrease in cytokine signaling during the peak period of synaptogenesis and spine formation and an increase during periods of activity-dependent developmentand early adulthood. Overall, the oscillating, age-dependent cytokine receptor alterations in the FC of MIA offspring identified here may have diagnostic and therapeutic value for neuropsychiatric disorders with a neuro-immune etiology.

A chronic mouse model of myocardial ischemia-reperfusion: essential in cytokine studies

2000 ◽  
Vol 278 (4) ◽  
pp. H1049-H1055 ◽  
Author(s):  
T. O. Nossuli ◽  
V. Lakshminarayanan ◽  
G. Baumgarten ◽  
G. E. Taffet ◽  
C. M. Ballantyne ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion ◽  
Rnase Protection Assay ◽  
Surgical Trauma ◽  
Mrna Levels ◽  
Rnase Protection ◽  
Closed Chest ◽  
Cytokine Induction ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion

Reperfusion of the ischemic myocardium is associated with a cytokine cascade that reflects a cellular response to injury. We studied this cascade in the mouse and found that acute surgical trauma in sham-operated animals obscured early changes in cytokine induction that occur during myocardial ischemia-reperfusion (MI/R). Therefore, we utilized a new implantable device that allows occlusion and reperfusion of the left anterior descending coronary artery in a closed-chest mouse at any time after instrumentation. Induction of interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNA in the whole heart was examined by RNase protection assay and quantitated by Phosphor- Imager. At 3 h after instrumentation, levels of IL-6 mRNA in sham-operated animals increased above those of control naive hearts, whereas this increase did not occur until after 1 day for TNF-α mRNA. The surgical trauma led to exaggeration of I/R cytokine induction with greater variance in response. At 3 days and 1 wk after instrumentation, levels of both IL-6 and TNF-α mRNA in sham-operated animals were comparable to those of naive hearts and induction responses in I/R were much less variant. We also found that 1 h of ischemia and 2 h of reperfusion at all time points of recovery (i.e., 3 h and 1, 3, and 7 days after instrumentation) led to a significant increase in IL-6 and TNF-α mRNA levels. In addition, 3 h of permanent occlusion, which did not induce any mRNA increase after 1 wk postinstrumentation, caused marked upregulation of IL-6 mRNA in an acutely prepared animal. This study of early cytokine responses evoked by MI/R highlights the need for dissipation of acute surgical trauma by using a chronic, closed-chest mouse preparation.

scholarly journals Is programming of glucocorticoid receptor expression by prenatal dexamethasone in the rat secondary to metabolic derangement in adulthood?

2003 ◽  
pp. 129-138 ◽  
Author(s):  
ME Cleasby ◽  
DE Livingstone ◽  
MJ Nyirenda ◽  
BR Walker ◽  
Keyword(s):  
Skeletal Muscle ◽  
Glucocorticoid Receptors ◽  
Rnase Protection Assay ◽  
Receptor Expression ◽  
Pregnant Rats ◽  
Corticosterone Concentration ◽  
Metabolic Derangement ◽  
Rnase Protection ◽  
Insulin Resistant ◽  
Design And Methods

OBJECTIVE: Glucocorticoids may contribute to the association between retarded growth in utero and insulin resistance in adulthood. Administration of dexamethasone (dex) to pregnant rats results in low birth weight offspring, which develop glucose intolerance, hyperinsulinaemia and hypercorticosteronaemia. This may be explained by tIssue-specific differences in expression of glucocorticoid receptors (GR) in adult offspring: GR is increased in visceral fat and liver, and decreased in hippocampus and soleus muscle. However, cause and effect between altered GR expression, hypercorticosteronaemia, and hyperinsulinaemia remains to be established. DESIGN AND METHODS: Rats were treated with dex (100 microg/kg per day) or saline during the third week of pregnancy. In 5-8-Month-old male offspring, GR expression in insulin target tIssues was quantified by RNase protection assay in rats that were adrenalectomised (ADX group), sham operated (SHAM group), or adrenalectomised with supra-physiological corticosterone replacement (CORT group) (n=7-8 per group), and in rats treated orally with vehicle, metformin (43 mg/kg per day) or rosiglitazone (1 mg/kg per day), after 3 weeks. RESULTS: Manipulation of corticosterone concentration did not affect GR mRNA in skeletal muscle or adipose. In liver, sham-operated animals showed lower GR mRNA, but there was no difference between adrenalectomised and hypercorticosteronaemic animals (SHAM 0.11+/-0.01 ratio to beta-actin, vs ADX 0.22+/-0.02, CORT 0.23+/-0.02, (values expressed as means+/-s.e.m.), P<0.001). Rosiglitazone reduced GR mRNA by approximately 30% in liver of dex- and saline-treated offspring (P<0.05), but had no effect on GR in adipose and skeletal muscle. Metformin abolished the 38% up-regulation of liver GR mRNA induced by antenatal dex and also reduced GR mRNA preferentially in muscle of dex-treated animals (0.14+/-0.01 vs 0.10+/-0.01; P=0.03). CONCLUSIONS: We conclude that neither hypercorticosteronaemia nor hyperinsulinaemia are sufficient to cause the changes in GR expression in dex-programmed rats, implying that these changes may be primary in determining the programmed insulin resistant phenotype. Normalisation of GR expression by metformin may be important in the mode of action of this anti-diabetic agent and may be especially useful to reverse-programmed up-regulation of GR.

Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect

2002 ◽  
Vol 283 (1) ◽  
pp. L94-L102 ◽  
Author(s):  
Weixiong Huang ◽  
Guirong Wang ◽  
David S. Phelps ◽  
Hamid Al-Mondhiry ◽  
Joanna Floros
Keyword(s):  
Pulmonary Fibrosis ◽  
Cytokine Production ◽  
Rnase Protection Assay ◽  
Protein A ◽  
Surfactant Protein ◽  
Pulmonary Complications ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rnase Protection ◽  
Tnf Α ◽  
Cytokine Levels

Surfactant protein A (SP-A) plays a role in host defense and inflammation in the lung. In the present study, we investigated the hypothesis that SP-A is involved in bleomycin-induced pulmonary fibrosis. We studied the effects of human SP-A on bleomycin-induced cytokine production and mRNA expression in THP-1 macrophage-like cells and obtained the following results. 1) Bleomycin-treated THP-1 cells increased tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-1β production in dose- and time-dependent patterns, as we have observed with SP-A. TNF-α levels were unaffected by treatment with cytosine arabinoside. 2) The combined bleomycin-SP-A effect on cytokine production is additive by RNase protection assay and synergistic by enzyme-linked immunosorbent assay. 3) Although the bleomycin effect on cytokine production was not significantly affected by the presence of surfactant lipid, the additive and synergistic effect of SP-A-bleomycin on cytokine production was significantly reduced. We speculate that the elevated cytokine levels resulting from the bleomycin-SP-A synergism are responsible for bleomycin-induced pulmonary fibrosis and that surfactant lipids can help ameliorate pulmonary complications observed during bleomycin chemotherapy.

Study on the Membrane Hemopoietic Cytokine Receptor Expression on CD34+ Bone Marrow Cells of the Patients with Myelodysplastic Syndromes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2908-2908
Author(s):  
Zonghong Shao ◽  
Lijuan Li ◽  
Rong Fu ◽  
Huaquan Wang ◽  
Lanzhu Yue ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Bone Marrow Cells ◽  
Low Risk ◽  
Receptor Expression ◽  
Cytokine Receptor ◽  
Cytokine Receptors ◽  
Control Group ◽  
The Mean ◽  
Marrow Cells

Abstract Abstract 2908 Objectives This study was to detect if there were abnormalities of membrane hemopoietic cytokine receptor expression on CD34+ bone marrow cells in MDS. Methods 34 newly diagnosed MDS(12 in low-risk and 22 in high-risk) cases and 32 normal controls were enrolled in this study. Their CD34+CD38+ and CD34+CD38- bone marrow cells and the expressions of stem cell factor receptor(SCF-R),erythropoietin receptor (EpoR), granulocyte colony-stimulating factor receptor (G-CSFR) and thrombopoietin receptor (TpoR) on those cells were measured by flow cytometry. Results The mean percentage of CD34+ BMMNCs of MDS cases in high risk[(2.94±4.79)%)] was significantly higher than that of control group[(0.95±1.06)%](P<0.05). The mean percentages of CD34+CD38+ cells were significantly lower in low risk and high risk groups[(86.98±6.83)% and (83.57±9.86)% respectively] than that in control group [(92.41±3.43)%], thus the percentage of CD34+CD38- cells was significantly higher in either low-risk or high-risk group[(13.03±6.84)% and (16.42±9.85)% respectively]than that in control group[(7.59±3.43)%](P<0.05). In control group, the mean percentage of antigen expression of EpoR was significantly lower in CD34+CD38+ cells [(17.72±20.24) %] than that in CD34+CD38- cells [(64.65±21.02)%](P<0.01), The expressions of SCF-R,G-CSFR and TpoR on CD34+CD38- cells were not significantly different from these on CD34+CD38+ cells. The expression of EpoR on CD34+CD38+ cells of low-risk and high-risk MDS groups[(7.01±6.82)% and (7.16±9.45)% respectively] were significantly lower than that of control group[(17.72±20. 24) %] (P<0.05), The expression of G-CSFR on CD34+CD38+ cells of low-risk and high-risk MDS groups[(22.65±12.14)% and (26.50±19.65)% respectively] were significantly lower than that of control group[(45.13±23.41)%](P<0.01). The amount of EpoR on CD34+CD38-cells of low-risk and high-risk MDS groups[(40.18±20.38)% and (28.58±17.00)% respectively] were significantly lower than that of control group[(64.65±21.02)%](P<0.01), The expression of TpoR on CD34+CD38- cells of low-risk and high-risk MDS groups[(4.46±7.45)% and (3.23±4.55)% respectively] were significantly lower than that of control group[(15.33±14.95)%](P<0.01). The incidence of cytopenia of MDS cases with low expression rates of hemopoietic cytokine receptors on CD34+cells were higher than that of MDS with high expression rates of hemopoietic cytokine receptors. Conclusions There were abnormalities of differentiation and membrane hemopoietic cytokine receptors expression of CD34+ bone marrow cells in MDS, which were associated with MDS cytopenia and might be useful for MDS diagnosis. Disclosures: No relevant conflicts of interest to declare.

Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-α-induced oxidant stress

1999 ◽  
Vol 276 (6) ◽  
pp. L979-L988 ◽  
Author(s):  
Edward G. Barrett ◽  
Carl Johnston ◽  
Günter Oberdörster ◽  
Jacob N. Finkelstein
Keyword(s):  
Epithelial Cells ◽  
Oxidant Stress ◽  
Rnase Protection Assay ◽  
Alveolar Type ◽  
Mrna Levels ◽  
Ros Production ◽  
Type Ii ◽  
Acetoxymethyl Ester ◽  
Rnase Protection ◽  
Tnf Α

We have shown previously that epithelial cells may contribute to the inflammatory response in the lung after exposure to crystalline silica through the production of and response to specific chemokines and cytokines. However, the exact cellular and molecular responses of epithelial cells to silica exposure remain unclear. We hypothesize that non-oxidant-mediated silica-cell interactions lead to the upregulation of tumor necrosis factor-α (TNF-α), whereby TNF-α-induced generation of reactive oxygen species (ROS) leads to the activation of the monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 genes. Using a murine alveolar type II cell line, murine lung epithelial (MLE)-15, we measured the early changes in TNF-α, MCP-1, and MIP-2 mRNA species after exposure of the cells to 18 μg/cm2 silica (cristobalite) in combination with various antioxidants. Total mRNA was isolated and assayed using an RNase protection assay after 6 h of particle exposure. We found that extracellular GSH could completely attenuate the cristobalite-induced expression of MCP-1 and MIP-2 mRNAs, whereas TNF-α mRNA levels were unaltered. We also found using the oxidant-sensitive dye 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate di(acetoxymethyl ester) that treatment of MLE-15 cells with cristobalite and TNF-α (1 ng/ml) resulted in ROS production. This ROS production could be inhibited with extracellular GSH treatment, and in the case of cristobalite-induced ROS, inhibition was also achieved with an anti-TNF-α antibody. The results support the hypothesis that TNF-α mediates cristobalite-induced MCP-1 and MIP-2 expression through the generation of ROS.

scholarly journals Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon

Gut ◽  
1999 ◽  
Vol 44 (5) ◽  
pp. 704-708 ◽  
Author(s):  
S Freier ◽  
O Weiss ◽  
M Eran ◽  
A Flyvbjerg ◽  
R Dahan ◽  
...  
Keyword(s):  
Growth Factors ◽  
Normal Tissue ◽  
Rnase Protection Assay ◽  
Receptor Expression ◽  
Adjacent Normal Tissue ◽  
Malignant Tissue ◽  
Rnase Protection ◽  
Igf I ◽  
Adenocarcinoma Of The Colon ◽  
Insulin Like Growth Factors

AIMSTo study changes in the expression of insulin-like growth factors (IGFs) and their receptors, as well as production of the IGF-I and IGF-II polypeptides, in adenocarcinoma of the colon.METHODSMalignant tissue obtained at operation was used. Total RNA was extracted and specific IGF-I and IGF-II and their receptor mRNAs were measured by a solution hybridisation RNase protection assay. IGF-I and IGF-II polypeptides were measured by specific immunoassays.RESULTSAll normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the polypeptide was present in small but equal amounts in normal and malignant tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in adjacent normal tissue and the concentration of the corresponding polypeptide was twice as high in the malignant tissue. IGF-I receptor expression was increased by a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4.CONCLUSIONSThis study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel.

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