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Association between IL-1beta/TNF-alpha-induced glucocorticoid-sensitive changes in multiple gene expression and altered responsiveness in airway smooth muscle.

https://arctichealth.org/en/permalink/ahliterature10091
Source
Am J Respir Cell Mol Biol. 2001 Dec;25(6):761-71
Publication Type
Article
Date
Dec-2001
Author
H. Hakonarson
E. Halapi
R. Whelan
J. Gulcher
K. Stefansson
M M Grunstein
Author Affiliation
DeCode Genetics, Reykjavik, Iceland. hakonh@decode.is
Source
Am J Respir Cell Mol Biol. 2001 Dec;25(6):761-71
Date
Dec-2001
Language
English
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Animals
Asthma - physiopathology
Comparative Study
Dexamethasone - pharmacology
Gene Expression Profiling
Gene Expression Regulation - drug effects
Interleukin-1 - pharmacology
Isoproterenol - pharmacology
Muscle Contraction - drug effects
Muscle Relaxation - drug effects
Muscle, Smooth - cytology - drug effects - metabolism
Oligonucleotide Array Sequence Analysis
RNA, Messenger - biosynthesis
Rabbits
Research Support, U.S. Gov't, P.H.S.
Signal Transduction - drug effects - physiology
Trachea - cytology - drug effects - metabolism
Transcription Factors - genetics - metabolism
Tumor Necrosis Factor-alpha - pharmacology
Abstract
The pleiotropic cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha have been implicated in the pathophysiology of asthma. To elucidate the role of these cytokines in the pro-asthmatic state, the effects of IL-1beta and TNF-alpha on airway smooth muscle (ASM) responsiveness and ASM expression of multiple genes, assessed by high-density oligonucleotide array analysis, were examined in the absence and presence of the glucocorticoid dexamethasone (DEX). Administration of IL-1beta/TNF-alpha increased ASM contractility to acetylcholine and impaired ASM relaxation to isoproterenol. These pro-asthmatic- like changes in ASM responsiveness were associated with IL-1beta/ TNF-alpha-induced mRNA expression of a host of proinflammatory genes that regulate transcription, cytokines and chemokines, cellular adhesion molecules, and various signal transduction molecules that regulate ASM responsiveness. In the presence of DEX, the changes induced in ASM responsiveness were abrogated, and most of the IL-1beta/TNF-alpha-mediated changes in proinflammatory gene expression were repressed, although mRNA expression of a small number of genes was enhanced by DEX. Collectively, the observations support the concept that, together with its role as a regulator of airway tone, in response to IL-1beta/TNF-alpha, the ASM expresses a host of glucocorticoid-sensitive genes that contribute to the altered structure and function of the airways in the pro-asthmatic state. We speculate that glucocorticoid-sensitive, cytokine-induced pathways involved in ASM cell signaling represent important targets for new therapeutic interventions.
PubMed ID
11726403 View in PubMed
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Degree of lung maturity determines the direction of the interleukin-1- induced effect on the expression of surfactant proteins.

https://arctichealth.org/en/permalink/ahliterature63986
Source
Am J Respir Cell Mol Biol. 2000 Mar;22(3):280-8
Publication Type
Article
Date
Mar-2000
Author
V. Glumoff
O. Väyrynen
T. Kangas
M. Hallman
Author Affiliation
Department of Pediatrics and Biocenter Oulu, University of Oulu, Oulu, Finland.
Source
Am J Respir Cell Mol Biol. 2000 Mar;22(3):280-8
Date
Mar-2000
Language
English
Publication Type
Article
Keywords
Amniotic Fluid - chemistry
Animals
Blotting, Western
Cycloheximide - pharmacology
Dactinomycin - pharmacology
Female
Fetus - chemistry - physiology
Gene Expression Regulation, Developmental - drug effects - physiology
Interleukin-1 - pharmacology
Lung - chemistry - growth & development - physiology
Organ Culture Techniques
Pregnancy
Protein Synthesis Inhibitors - pharmacology
Proteolipids - analysis - genetics
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants - analysis - genetics
RNA, Messenger - analysis - genetics
Rabbits
Research Support, Non-U.S. Gov't
Abstract
Intra-amniotic interleukin (IL)-1 increases surfactant components in immature fetal lung, whereas high IL-1 after birth is associated with surfactant dysfunction. Our aim was to investigate whether the fetal age influences the responsiveness of surfactant proteins (SPs) to IL-1. Rabbit lung explants from fetuses at 19, 22, 27, and 30 d of gestation and 1-d-old newborns were cultured in serum-free medium in the presence of recombinant human (rh) IL-1alpha or vehicle. The influence of IL-1alpha on SP-A, -B, and -C messenger RNA (mRNA) content was dependent on the conceptional age. In very immature lung on Day 19, rhIL-1alpha (570 ng/ml for 20 h) increased SP-A, -B, and -C mRNA by 860+/-15%, 314+/-108%, and 64+/-17%, respectively. The increase in SP-A mRNA was evident within 4 to 6 h. IL-1alpha increased the SP-A concentration in alveolar epithelial cells and in the culture medium within 20 h. In contrast, at 27 to 30 d of gestation and in newborns, IL-1alpha decreased SP-C, -B, and -A mRNA by means of 64 to 67%, 48 to 59%, and 12 to 15%, respectively. SP-B protein decreased by 45 to 60%. The decrease in mRNA became evident within 8 to 12 h and was dependent on IL-1 concentration. On Day 27, IL-1alpha accelerated the degradation of SP-B mRNA in the presence of actinomycin D. IL-1 did not increase the degradation rate of SP-A mRNA unless both actinomycin D and cycloheximide were added to the explants. The present findings may explain some of the contrasting associations between inflammatory cytokines and lung diseases during the perinatal period. The determinants of the direction of the IL-1 effect on the expression of SPs remain to be identified.
PubMed ID
10696064 View in PubMed
Less detail

Effect of interleukin-1 beta on airway hyperresponsiveness and inflammation in sensitized and nonsensitized Brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature57706
Source
J Allergy Clin Immunol. 1994 Feb;93(2):464-9
Publication Type
Article
Date
Feb-1994
Author
H. Tsukagoshi
T. Sakamoto
W. Xu
P J Barnes
K F Chung
Author Affiliation
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, England.
Source
J Allergy Clin Immunol. 1994 Feb;93(2):464-9
Date
Feb-1994
Language
English
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Airway Resistance - drug effects - physiology
Animals
Bradykinin - pharmacology
Bronchial Hyperreactivity - etiology - pathology - physiopathology
Bronchoalveolar Lavage Fluid - cytology
Immunization
Inflammation - etiology - physiopathology
Interleukin-1 - pharmacology
Male
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Time Factors
Abstract
Airway responsiveness (AR) to inhaled acetylcholine and bradykinin and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred male Brown-Norway rats actively sensitized to ovalbumin and later given 500 U interleukin-1 beta (IL-1 beta) intratracheally. We examined animals 14 to 21 days after initial sensitization at 18 to 24 hours after the intratracheal administration of IL-1 beta. We evaluated AR to acetylcholine as -log PC200, which is -log10 transformation of provocative concentration of acetylcholine producing 200% increase in lung resistance, and to bradykinin as percent increase in lung resistance. BALF was examined as an index of inflammatory changes within the lung. Although there was no significant difference in baseline lung resistance, nonsensitized and sensitized animals that were given IL-1 beta demonstrated a significant increase of AR to bradykinin at 18 to 24 hours and a significant increase of neutrophil counts in BALF, which was already observed by 4 to 6 hours. There was a significant correlation between AR to bradykinin and neutrophil counts in BALF in all animals (r = 0.644; p
PubMed ID
8120273 View in PubMed
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Genetically determined differences in newborn rat islet sensitivity to interleukin-1 in vitro: no association with the diabetes prone phenotype in the BB-rat.

https://arctichealth.org/en/permalink/ahliterature48773
Source
Acta Endocrinol (Copenh). 1989 Jan;120(1):92-8
Publication Type
Article
Date
Jan-1989
Author
H U Andersen
T. Mandrup-Poulsen
J. Egeberg
S. Helqvist
J. Nerup
Author Affiliation
Steno Memorial Hospital, Gentofte, Denmark.
Source
Acta Endocrinol (Copenh). 1989 Jan;120(1):92-8
Date
Jan-1989
Language
English
Publication Type
Article
Keywords
Animals
Cells, Cultured
Comparative Study
DNA - analysis
Diabetes Mellitus, Type 1 - genetics
Insulin - secretion
Interleukin-1 - pharmacology
Islets of Langerhans - drug effects - pathology
Phenotype
Rats
Rats, Inbred BB - genetics
Rats, Inbred BN
Rats, Inbred Lew
Rats, Inbred Strains - genetics
Rats, Inbred WF
Research Support, Non-U.S. Gov't
Abstract
This study was designed to investigate whether the genetic predisposition to insulin-dependent diabetes mellitus (IDDM) might be caused by an inherited increased sensitivity of the pancreatic B-cells to immune effector molecules e.g. the monokine interleukin 1 (IL-1), which is selectively cytotoxic to B-cells in vitro. Islets of Langerhans isolated from newborn diabetes prone and diabetes resistant Bio-Breeding rats, as well as from the inbred non-diabetic rat strains Wistar Furth, Brown-Norway and Lewis-Scripps were exposed to 0-1000 ng/l [corrected] of recombinant human IL-1 beta for 7 days. Strain-related differences in the sensitivity to IL-1 were studied by comparing the dose-responses of insulin release at 11 mmol/l glucose and islet light microscopic morphology to varying concentrations of IL-1. Statistical analyses showed a significant impact of strain on B-cell sensitivity to IL-1, Brown-Norway islets being relatively resistant to the action of IL-1. However, the the diabetes prone islets were not more sensitive to the cytotoxic effect of IL-1 than the non-diabetic control strain islets. We conclude that genetic differences in the response to IL-1 exist in vitro, but that this phenomenon is unrelated to the propensity to develop IDDM.
Notes
Erratum In: Acta Endocrinol (Copenh) 1989 Mar;120(3):400
PubMed ID
2643251 View in PubMed
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Inflammatory and anti-inflammatory responsiveness of surfactant proteins in fetal and neonatal rabbit lung.

https://arctichealth.org/en/permalink/ahliterature58347
Source
Pediatr Res. 2004 Jan;55(1):55-60
Publication Type
Article
Date
Jan-2004
Author
Outi Vayrynen
Virpi Glumoff
Mikko Hallman
Author Affiliation
Department of Pediatrics and Biocenter Oulu, University of Oulu, Kajaanintie 52, 90220 Oulu, Finland. mikko.hallman@oulu.fi
Source
Pediatr Res. 2004 Jan;55(1):55-60
Date
Jan-2004
Language
English
Publication Type
Article
Keywords
Adrenal Cortex Hormones - pharmacology
Animals
Animals, Newborn
Dexamethasone - pharmacology
Female
Gene Expression - drug effects
Humans
Infant, Newborn
Interleukin-1 - pharmacology
Lung - embryology - immunology
Organ Culture Techniques
Pneumonia - drug therapy - immunology
Pregnancy
Pulmonary Surfactant-Associated Protein A - genetics
Pulmonary Surfactant-Associated Protein B - genetics
Pulmonary Surfactant-Associated Protein C - genetics
RNA, Messenger - analysis
Rabbits
Research Support, Non-U.S. Gov't
Respiratory Distress Syndrome, Newborn - drug therapy - immunology
Abstract
Spontaneous preterm birth due to intrauterine infection is associated with increased concentrations of cytokines in amniotic fluid and in the airways at birth. Intra-amniotic IL-1 induces fetal lung maturity, consistent with the decrease in the incidence of respiratory distress syndrome (RDS) in intrauterine inflammation. On the other hand, antenatal corticosteroid decreases the incidence of RDS in infants born prematurely. The aim of the present study was to investigate the interaction between IL-1 and glucocorticoid in the expression of the surfactant proteins SP-A, -B, and -C. Lung explants from rabbit fetuses at 22 (immature), 27 (transitional), and 30 (mature) d of gestation (term, 30-31 d) and on d 1 after term birth were cultured with dexamethasone (Dx), IL-1alpha, or vehicle in the presence or absence of actinomycin D. According to the present results, IL-1alpha and Dx additively increased the expression of SP-A and SP-B on d 22. Later in gestation, SP-B and SP-C were suppressed by IL-1, whereas glucocorticoid tended to increase the expression of SP-B and SP-C and prevented the IL-1-induced suppression of SP. IL-1alpha and steroid interactively increased the stability of SP mRNA compared with the single agonist, possibly explaining the additive effects on the SP mRNA levels. The present results reveal beneficial additive effects of glucocorticoid and cytokine on lung surfactant. They may explain some of the acute beneficial effects of glucocorticoid therapy in chorioamnionitis before premature birth and in inflammatory lung disease after birth.
PubMed ID
14605255 View in PubMed
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Mechanisms of down-regulation of CYP2E1 expression by inflammatory cytokines in rat hepatoma cells.

https://arctichealth.org/en/permalink/ahliterature18590
Source
J Pharmacol Exp Ther. 2003 Mar;304(3):1048-54
Publication Type
Article
Date
Mar-2003
Author
Jukka Hakkola
Yin Hu
Magnus Ingelman-Sundberg
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland. jukka.hakkola@oulu.fi
Source
J Pharmacol Exp Ther. 2003 Mar;304(3):1048-54
Date
Mar-2003
Language
English
Publication Type
Article
Keywords
Animals
Carcinoma, Hepatocellular - pathology
Cytochrome P-450 CYP2E1 - genetics - metabolism
Cytokines - pharmacology
DNA-Binding Proteins
Down-Regulation
Gene Expression Regulation - drug effects
Hepatocyte Nuclear Factor 1
Hepatocyte Nuclear Factor 1-alpha
Hepatocyte Nuclear Factor 1-beta
Hepatocytes - drug effects - metabolism
Interleukin-1 - pharmacology
Interleukin-6 - pharmacology
Nuclear Proteins
Promoter Regions (Genetics) - drug effects - genetics
Rats
Research Support, Non-U.S. Gov't
Trans-Activation (Genetics)
Transcription Factors - metabolism
Transcription, Genetic - drug effects
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - pharmacology
Abstract
CYP2E1 is one of the major cytochrome P450 forms whose expression is strongly inhibited by inflammatory cytokines in humans and rodents. In the present study, we have used the Fao rat hepatoma cell line that constitutively expresses CYP2E1 enzyme to investigate mechanisms of cytokine action. The cells were treated with interleukin (IL)-1beta, tumor necrosis factor-alpha (TNFalpha), or IL-6 for 24 or 72 h, and the expression of CYP2E1 was monitored at the transcriptional, mRNA, and protein levels. All three cytokines decreased the CYP2E1 mRNA levels after 24 h, and the effect was even stronger after 72 h. In contrast, significant inhibition of CYP2E1 protein was seen only after 72 h. In transfection assays using a CYP2E1 5' -3685 to +29-luciferase construct, it was found that IL-6 inhibited gene transcription after 24 h, but a similar effect by IL-1beta and TNFalpha was registered only after 72 h. Using 5' deletions of the CYP2E1 5'-reporter construct a responsive region for the IL-6 effect was located to -669 to -507 base pairs in the CYP2E1 5'-flanking region. Interestingly, IL-1beta, but not TNFalpha, was found to reduce hepatocyte nuclear factor (HNF)-1alpha binding to the CYP2E1 promotor. However, the transactivation function of HNF-1alpha was found to be impaired in Fao cells. In mouse primary hepatocytes, IL-1beta decreased HNF-1alpha-mediated transactivation. In conclusion, our data indicate that inflammatory cytokines inhibit CYP2E1 expression by multiple mechanisms, including control of HNF-1alpha function and regulation of other transcriptional factors acting on the CYP2E1 5'-upstream regulatory region. In addition, regulation of factors of importance for the CYP2E1 mRNA stability may be involved.
PubMed ID
12604681 View in PubMed
Less detail

Mechanisms of impaired beta-adrenoceptor-induced airway relaxation by interleukin-1beta in vivo in the rat.

https://arctichealth.org/en/permalink/ahliterature11157
Source
J Clin Invest. 1996 Oct 15;98(8):1780-7
Publication Type
Article
Date
Oct-15-1996
Author
H. Koto
J C Mak
E B Haddad
W B Xu
M. Salmon
P J Barnes
K F Chung
Author Affiliation
Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Source
J Clin Invest. 1996 Oct 15;98(8):1780-7
Date
Oct-15-1996
Language
English
Publication Type
Article
Keywords
Animals
Autoradiography
Bronchi - drug effects - physiology
Cyclic AMP - metabolism
Forskolin - pharmacology
GTP-Binding Proteins - analysis
Interleukin-1 - pharmacology
Isoproterenol - pharmacology
Muscle Relaxation - drug effects
RNA, Messenger - analysis
Rats
Rats, Inbred BN
Receptors, Adrenergic, beta - analysis - genetics - physiology
Research Support, Non-U.S. Gov't
Trachea - drug effects - physiology
Abstract
We studied the in vivo mechanism of beta-adrenergic receptor (beta-AR) hyporesponsiveness induced by intratracheal instillation of interleukin-1beta (IL-1beta, 500 U) in Brown-Norway rats. Tracheal and bronchial smooth muscle responses were measured under isometric conditions ex vivo. Contractile responses to electrical field stimulation and to carbachol were not altered, but maximal relaxation induced by isoproterenol (10(-6)-10(-5) M) was significantly reduced 24 h after IL-1beta treatment in tracheal tissues and to a lesser extent, in the main bronchi. Radioligand binding using [125I]iodocyanopindolol revealed a 32+/-7% reduction in beta-ARs in lung tissues from IL-1beta-treated rats, without any significant changes in beta2-AR mRNA level measured by Northern blot analysis. Autoradiographic studies also showed significant reduction in beta2-AR in the airways. Isoproterenol-stimulated cyclic AMP accumulation was reduced by IL-1beta at 24 h in trachea and lung tissues. Pertussis toxin reversed this hyporesponsiveness to isoproterenol but not to forskolin in lung tissues. Western blot analysis revealed an IL-1beta-induced increase in Gi(alpha) protein expression. Thus, IL-1beta induces an attenuation of beta-AR-induced airway relaxation through mechanisms involving a reduction in beta-ARs, an increase in Gi(alpha) subunit, and a defect in adenylyl cyclase activity.
PubMed ID
8878428 View in PubMed
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Regulation of surfactant proteins by LPS and proinflammatory cytokines in fetal and newborn lung.

https://arctichealth.org/en/permalink/ahliterature58538
Source
Am J Physiol Lung Cell Mol Physiol. 2002 Apr;282(4):L803-10
Publication Type
Article
Date
Apr-2002
Author
Outi Väyrynen
Virpi Glumoff
Mikko Hallman
Author Affiliation
Department of Pediatrics, Biocenter Oulu, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. ovayryne@paju.oulu.fi
Source
Am J Physiol Lung Cell Mol Physiol. 2002 Apr;282(4):L803-10
Date
Apr-2002
Language
English
Publication Type
Article
Keywords
Acute Disease
Animals
Animals, Newborn
Antineoplastic Agents - pharmacology
Female
Gene Expression - drug effects - immunology
Humans
Infant, Newborn
Interferon Type II - pharmacology
Interleukin-1 - pharmacology
Lipopolysaccharides - pharmacology
Lung - growth & development - immunology - metabolism
Organ Culture Techniques
Pregnancy
Proteolipids - genetics - metabolism
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants - genetics - metabolism
RNA, Messenger - analysis
Rabbits
Research Support, Non-U.S. Gov't
Respiratory Distress Syndrome, Newborn - immunology - metabolism
Tumor Necrosis Factor-alpha - pharmacology
Abstract
Intra-amniotic lipopolysaccharide (LPS) and cytokines may decrease respiratory distress syndrome (RDS) and increase chronic lung disease in the newborn. The aim was to identify the primary inflammatory mediators regulating the expression of surfactant proteins (SP) in explants from immature (22-day-old fetus) and mature (30-day term fetus and 2-day-old newborn) rabbits. In immature lung, interleukin (IL)-1alpha and IL-1beta upregulated the expression of SP-A and SP-B. These effects of IL-1 were diminished, and SP-C mRNA was suppressed additively in the presence of tumor necrosis factor (TNF)-alpha and either LPS or interferon (IFN)-gamma. LPS, TNF-alpha, or IFN-gamma had no effect alone. In explants from the term fetus and the newborn, LPS, IL-1alpha, and TNF-alpha additively suppressed the SPs. LPS acutely induced IL-1alpha in alveolar macrophages in mature lung but not in the immature lung. IFN-gamma that generally has low expression in intrauterine infection decreased the age dependence of the other agonists' effects on SPs. The present study serves to explain the variation of the pulmonary outcome after an inflammatory insult. We propose that IL-1 from extrapulmonary sources induces the SPs in premature lung and is responsible for the decreased risk of RDS in intra-amniotic infection.
PubMed ID
11880307 View in PubMed
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Upregulation of tumour endothelial marker-8 by interleukin-1beta and its impact in IL-1beta induced angiogenesis.

https://arctichealth.org/en/permalink/ahliterature179610
Source
Int J Mol Med. 2004 Jul;14(1):75-80
Publication Type
Article
Date
Jul-2004
Author
Khaled A Rmali
Mahir A A Al-Rawi
Christian Parr
Malcolm C A Puntis
Wen G Jiang
Author Affiliation
Metastasis and Angiogenesis Research Group, University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK. rmali@cf.ac.uk
Source
Int J Mol Med. 2004 Jul;14(1):75-80
Date
Jul-2004
Language
English
Publication Type
Article
Keywords
Endothelium, Vascular - chemistry - cytology - drug effects
Humans
Interleukin-1 - pharmacology
Membrane Proteins
Neoplasm Proteins
Neovascularization, Pathologic - metabolism
RNA, Messenger - analysis
Receptors, Cell Surface - analysis - biosynthesis - genetics
Tumor Markers, Biological - metabolism
Up-Regulation
Abstract
Tumour endothelial marker-8 (TEM-8) has been found to be selectively upregulated in tumour-associated endothelial cells and is implicated in tumour specific angiogenesis. Specific factors, indigenous to tissues and tumours that regulate the TEM-8 mechanism in angiogenesis are not defined. We report for the first time that interleukin-1beta induces the expression of TEM-8 in endothelial cells. Human vascular endothelial cells (HECV), which strongly express IL-1beta receptor (as revealed by RT-PCR, Western blotting), increased the level of TEM-8 expression following stimulation with IL-1beta (as revealed by conventional and quantitative RT-PCR). Using a newly developed antibody to human TEM-8, we have further demonstrated that IL-1beta significantly raised the level of TEM-8 at the protein level, as revealed by Western blotting. In vitro tubule forming assay, revealed that IL-1beta significantly induced the formation of capillary-like tubules from the HECV cells, accompanied by an increase in TEM-8 expression. It is concluded that IL-1beta is a powerful regulator of the expression of TEM-8 in vascular endothelial cells. Our results suggest an important pathway through which IL-1beta regulates tumour-associated angiogenesis.
PubMed ID
15202019 View in PubMed
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9 records – page 1 of 1.