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Book ; Thesis: Experimental animal mode for the study of inflammatory bowel diseases and gastrointestinal anti-inflammatory drugs

Axelsson, Lars-Göran

(Comprehensive summaries of Uppsala dissertations from the Faculty of Science and Technology ; 215 ; Acta Universitatis Upsaliensis)

1996

Author's details	by Lars-Göran Axelsson
Series title	Comprehensive summaries of Uppsala dissertations from the Faculty of Science and Technology ; 215 Acta Universitatis Upsaliensis
Collection
Language	English
Size	62 S. : Ill., graph. Darst.
Publisher	Almqvist & Wiksell
Publishing place	Stockholm
Publishing country	Sweden
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Uppsala, Univ., Diss., 1996
HBZ-ID	HT007601228
ISBN	9155437814 ; 9789155437817
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Immunomodulatory oligonucleotides inhibit neutrophil migration by decreasing the surface expression of interleukin-8 and leukotriene B4 receptors.

Admyre, Charlotte / Axelsson, Lars-Göran / von Stein, Oliver / Zargari, Arezou

Immunology

2014 Volume 144, Issue 2, Page(s) 206–217

Abstract: Neutrophils play important roles in many inflammatory diseases. The migration of neutrophils to the inflammatory site is tightly regulated by specific chemokines, of which interleukin-8 (IL-8) and leukotriene B4 (LTB4 ) constitute key mediators by ... ...

Abstract	Neutrophils play important roles in many inflammatory diseases. The migration of neutrophils to the inflammatory site is tightly regulated by specific chemokines, of which interleukin-8 (IL-8) and leukotriene B4 (LTB4 ) constitute key mediators by binding to the surface receptors CXCR1/2 and BLT1, respectively. Oligonucleotides (ODN) containing CpG motifs mediate potent immunomodulatory effects through binding to Toll-like receptor 9. So far, knowledge on how ODN can affect neutrophil migration during inflammation is lacking. This study demonstrates that several novel CpG ODN significantly down-regulate the surface expression of CXCR1/2 and BLT1. In addition, the ODN significantly blocked IL-8-induced and LTB4 -induced neutrophil migration in vitro, as well as leucocyte migration in vivo demonstrated in mice by intravital microscopy and in a model of airway inflammation. The down-regulation of CXCR1 is rapid, occurring 15 min after ODN stimulation, and can be mediated through an endosomally independent mechanism. Inhibition of the IL-8 and LTB4 pathways may provide new opportunities of therapeutic intervention using ODN to reduce neutrophil infiltration during inflammation.
MeSH term(s)	Animals ; Chemotaxis, Leukocyte/drug effects ; Chemotaxis, Leukocyte/immunology ; CpG Islands/genetics ; Down-Regulation/immunology ; Female ; Humans ; Immunologic Factors/pharmacology ; Immunomodulation ; Inflammation/drug therapy ; Inflammation/immunology ; Interleukin-8/antagonists & inhibitors ; Interleukin-8/biosynthesis ; Interleukin-8/immunology ; Macrophage-1 Antigen/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neutrophil Infiltration/drug effects ; Neutrophil Infiltration/immunology ; Neutrophils/drug effects ; Neutrophils/immunology ; Oligonucleotides/pharmacology ; Ovalbumin ; Receptors, Interleukin-8A/biosynthesis ; Receptors, Interleukin-8B/biosynthesis ; Receptors, Leukotriene B4/antagonists & inhibitors ; Receptors, Leukotriene B4/biosynthesis ; Receptors, Leukotriene B4/immunology ; Toll-Like Receptor 9/immunology ; Tumor Necrosis Factor-alpha/immunology
Chemical Substances	Immunologic Factors ; Interleukin-8 ; Macrophage-1 Antigen ; Oligonucleotides ; Receptors, Interleukin-8A ; Receptors, Interleukin-8B ; Receptors, Leukotriene B4 ; Toll-Like Receptor 9 ; Tumor Necrosis Factor-alpha ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2014-08-07
Publishing country	England
Document type	Journal Article
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.12368
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Book ; Thesis: Experimental animal models for the study of inflammatory bowel diseases and gastrointestinal anti-inflammatory drugs

Axelsson, Lars-Göran

(Acta Universitatis Upsaliensis : Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology ; 215)

1996

Author's details	by Lars-Göran Axelsson
Series title	Acta Universitatis Upsaliensis : Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology ; 215
Language	English
Size	62 S, Ill., graph. Darst
Publisher	AUU
Publishing place	Uppsala
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Uppsala, 1996
ISBN	9155437814 ; 9789155437817
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article: Selective expression of detoxifying glutathione transferases in mouse colon: effect of experimental colitis and the presence of bacteria.

Edalat, Maryam / Mannervik, Bengt / Axelsson, Lars-Göran

Histochemistry and cell biology

2004 Volume 122, Issue 2, Page(s) 151–159

Abstract: Glutathione transferases (GSTs) play a central role in the cellular defense against harmful endogenous compounds and xenobiotics in mouse and man. The gastrointestinal channel is constantly exposed to bacteria, bacterial products, and xenobiotics. In the ...

Abstract	Glutathione transferases (GSTs) play a central role in the cellular defense against harmful endogenous compounds and xenobiotics in mouse and man. The gastrointestinal channel is constantly exposed to bacteria, bacterial products, and xenobiotics. In the present study the distribution of alpha, mu, and pi class GSTs was examined immunohistologically in the colon of conventional and germ-free (GF) mice subjected to experimental colitis. The tissues samples were from conventional mice with and without colitis induced by dextran sulfate sodium (DSS); GF mice treated with DSS or carrageenan; and GF mice inoculated with normal mouse bacterial flora as well as with Lactobacillus GG. In conventional as well as in GF mice the mu and pi class GSTs showed reduced intestinal expression when colitis was induced. In con-rast, the level of GSTs reacting with antibodies directed against the alpha class, in particular mGST A4-4, was elevated after induction of inflammation. Of special interest is mGST A4-4 because of its high catalytic activity with toxic products of lipid peroxidation. In the colon of conventionalized GF mice that were given mouse intestinal flora, the mGST A4-4 expression was increased with time for several weeks, but then showed a decrease to a normal level. Additionally, the inoculation of GF mice with Lactobacillus GG induced all the intestinal GSTs studied.
MeSH term(s)	Animals ; Colitis/chemically induced ; Colitis/enzymology ; Colitis/microbiology ; Colon/enzymology ; Colon/microbiology ; Dextran Sulfate ; Gene Expression Regulation, Enzymologic/physiology ; Germ-Free Life ; Glutathione Transferase/biosynthesis ; Glutathione Transferase/metabolism ; Histocytochemistry ; Inactivation, Metabolic ; Isoenzymes/biosynthesis ; Isoenzymes/metabolism ; Lactobacillus/metabolism ; Mice
Chemical Substances	Isoenzymes ; Dextran Sulfate (9042-14-2) ; Glutathione Transferase (EC 2.5.1.18)
Language	English
Publishing date	2004-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1222930-1
ISSN	1432-119X ; 0948-6143 ; 0301-5564
ISSN (online)	1432-119X
ISSN	0948-6143 ; 0301-5564
DOI	10.1007/s00418-004-0688-7
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Article: Indigenous microbes and their soluble factors differentially modulate intestinal glycosylation steps in vivo. Use of a "lectin assay" to survey in vivo glycosylation changes.

Freitas, Miguel / Axelsson, Lars-Göran / Cayuela, Chantal / Midtvedt, Tore / Trugnan, Germain

Histochemistry and cell biology

2005 Volume 124, Issue 5, Page(s) 423–433

Abstract: It has been shown that Bacteroides thetaiotaomicron, a representative member of the gut microflora, signals intestinal epithelial cells both in vivo and in vitro and modulate specific glycosylation processes that may mediate intestinal functions. However ...

Abstract	It has been shown that Bacteroides thetaiotaomicron, a representative member of the gut microflora, signals intestinal epithelial cells both in vivo and in vitro and modulate specific glycosylation processes that may mediate intestinal functions. However it is not known whether these modulations depend on the presence of live bacteria or may be elicited by soluble factors produced in vitro by this bacterium. We used lectins and an histochemical approach to survey tissue sections prepared from various cellular compartments of the small and large intestine of NRMI/KI mice grown under gnotobiotic conditions. We compared the results obtained with bacterial culture supernatant and live B. thetaiotaomicron to those obtained from germ-free mice or mice having a conventional microflora. This approach allowed us to conclude that (1) a small but specific number of glycan patterns were restored after treatment with bacterial culture supernatant and (2) the B. thetaiotaomicron associated mice restored a larger number of patterns, however, the complete conventional mice pattern must be a function of the whole microflora in the gut. The possibility to modulate this complex glycosylation pattern by introducing exogenous bacteria and bacterial products should be considered as a promising approach towards understanding the molecular basis of microbial-host interactions.
MeSH term(s)	Animals ; Bacteroides/metabolism ; Binding Sites ; Enterocytes/cytology ; Enterocytes/metabolism ; Enterocytes/microbiology ; Female ; Germ-Free Life ; Glycosylation ; Image Processing, Computer-Assisted ; Intestinal Mucosa/cytology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology ; Intestine, Large/cytology ; Intestine, Large/metabolism ; Intestine, Large/microbiology ; Intestine, Small/cytology ; Intestine, Small/metabolism ; Intestine, Small/microbiology ; Male ; Mice ; Mice, Inbred Strains ; Microscopy, Confocal ; Plant Lectins/metabolism ; Signal Transduction
Chemical Substances	Plant Lectins
Language	English
Publishing date	2005-11
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1222930-1
ISSN	1432-119X ; 0948-6143 ; 0301-5564
ISSN (online)	1432-119X
ISSN	0948-6143 ; 0301-5564
DOI	10.1007/s00418-005-0004-1
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Article: Regulatory role of 5-HT and muscarinic receptor antagonists on the migrating myoelectric complex in rats.

Axelsson, Lars Göran / Wallin, Berndt / Gillberg, Per Göran / Sjöberg, Birger / Söderberg, Charlotte / Hellström, Per M

European journal of pharmacology

2003 Volume 467, Issue 1-3, Page(s) 211–218

Abstract: The 5-HT(3) and 5-HT(4) receptor antagonists alosetron and piboserod, and the muscarinic receptor antagonists PNU-171990A (2-(diisopropylamino)ethyl 1-phenylcyclopentanecarboxylate, hydrochloride) and PNU-174708A (2-(diisopropylamino)ethyl 1- ... ...

Abstract	The 5-HT(3) and 5-HT(4) receptor antagonists alosetron and piboserod, and the muscarinic receptor antagonists PNU-171990A (2-(diisopropylamino)ethyl 1-phenylcyclopentanecarboxylate, hydrochloride) and PNU-174708A (2-(diisopropylamino)ethyl 1-phenylcyclohexanecarboxylate) were studied by electromyography, defining the migrating myoelectric complex (MMC) after i.v. administration in conscious rats. Alosetron prolonged the MMC cycle length from 16.6 to maximally 30.4 min at the dose 0.5 mg kg(-1). Piboserod promptly abolished MMC pattern and prolonged cycle length from 16.5 to >60 min at 0.5 mg kg(-1). PNU-171990A and PNU-174708A had no effect on basal cycle length up to a dose of 20 mg kg(-1). In controls, saline did not change the MMC pattern, while L-hyoscyamine at the same dose, 20 mg kg(-1), prolonged cycle length from 17.6 to 29.0 min. None of the drugs affected duration or propagation velocity of phase III of MMC. Blockade of 5-HT(4) receptors seems to exert a powerful inhibitory effect on motility, 5-HT(3) receptor blockade is less efficient and muscarinic receptor blockade has low efficacy.
MeSH term(s)	Animals ; Atropine/pharmacology ; Carbolines/pharmacology ; Carboxylic Acids ; Cyclopropanes ; Dose-Response Relationship, Drug ; Electromyography ; Esters/pharmacology ; Indoles/pharmacology ; Intestine, Small/drug effects ; Intestine, Small/physiology ; Muscarinic Antagonists/pharmacology ; Myoelectric Complex, Migrating/drug effects ; Myoelectric Complex, Migrating/physiology ; Oxazines/pharmacology ; Rats ; Receptors, Muscarinic/drug effects ; Receptors, Muscarinic/physiology ; Receptors, Serotonin, 5-HT3/drug effects ; Receptors, Serotonin, 5-HT3/physiology ; Receptors, Serotonin, 5-HT4/drug effects ; Receptors, Serotonin, 5-HT4/physiology ; Serotonin Antagonists/pharmacology
Chemical Substances	2-(diisopropylamino)ethyl 1-phenylcyclopentanecarboxylate ; Carbolines ; Carboxylic Acids ; Cyclopropanes ; Esters ; Indoles ; Muscarinic Antagonists ; Oxazines ; Receptors, Muscarinic ; Receptors, Serotonin, 5-HT3 ; Serotonin Antagonists ; alosetron (13Z9HTH115) ; Receptors, Serotonin, 5-HT4 (158165-40-3) ; piboserod (4UQ3S81B25) ; Atropine (7C0697DR9I)
Language	English
Publishing date	2003-04-25
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/s0014-2999(03)01637-6
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Article: Abrogated lymphocyte infiltration and lowered CD14 in dextran sulfate induced colitis in mice treated with p65 antisense oligonucleotides.

Spiik, Ann-Kristin / Ridderstad, Anna / Axelsson, Lars-Göran / Midtvedt, Tore / Björk, Lars / Pettersson, Sven

International journal of colorectal disease

2002 Volume 17, Issue 4, Page(s) 223–232

Abstract: Background and aims: Dextran sulfate sodium (DSS) induced colitis exhibits a predominantly NF-kappaB dependent proinflammatory cytokine profile and shares similarities with human inflammatory bowel disease (IBD). Lamina propria macrophages of IBD ... ...

Abstract	Background and aims: Dextran sulfate sodium (DSS) induced colitis exhibits a predominantly NF-kappaB dependent proinflammatory cytokine profile and shares similarities with human inflammatory bowel disease (IBD). Lamina propria macrophages of IBD patients display elevated levels of NF-kappaB p65. Knowing the role of NF-kappaB in IBD, we investigated the beneficial cellular mechanisms underlying the lasting effect of a single p65 antisense treatment in DSS-colitis mice. Methods: One local dose of p65 antisense oligonucleotides was administered in DSS colitis mice. Ten days later the mice were killed and examined at cellular and biochemical levels. The level of p65 in lamina propria cells was determined by electrophoretic mobility shift assay and by intracellular immunofluorescent staining of nuclear p65 levels, using laser scanning cytometer. Results: FACS analysis demonstrated a considerable drop in infiltrating lymphocytes and a drastic reduction in CD14+ cells in mice treated with p65 antisense oligonucleotides. Moreover, abrogation of inflammation extended all the way to the cecum in treated mice. Treatment was correlated with decreased DNA binding activity of NF-kappaB. Conclusion: Our data strongly support a model in which p65 antisense treatment possesses the capacity to disrupt the pathogenic autocrine loop propagated by NF-kappaB at the chronic phase of IBD.
MeSH term(s)	Animals ; Colitis/chemically induced ; Colitis/immunology ; Colitis/therapy ; Dextran Sulfate ; Female ; Humans ; Lipopolysaccharide Receptors/immunology ; Lymphocytes/immunology ; Male ; Mice ; NF-kappa B/drug effects ; NF-kappa B/immunology ; Oligonucleotides, Antisense/therapeutic use ; Time Factors
Chemical Substances	Lipopolysaccharide Receptors ; NF-kappa B ; Oligonucleotides, Antisense ; Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2002-07
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-001-0366-3
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Article: Microbial-host interactions specifically control the glycosylation pattern in intestinal mouse mucosa.

Freitas, Miguel / Axelsson, Lars-Göran / Cayuela, Chantal / Midtvedt, Tore / Trugnan, Germain

Histochemistry and cell biology

2002 Volume 118, Issue 2, Page(s) 149–161

Abstract: The glycosylation of the intestinal cell layer is thought to control several key functions of the gut such as vectorial transports, defence against microbial agents or immunological processes. It has been assumed that the gut microflora may modulate the ... ...

Abstract	The glycosylation of the intestinal cell layer is thought to control several key functions of the gut such as vectorial transports, defence against microbial agents or immunological processes. It has been assumed that the gut microflora may modulate the glycosylation pattern of the intestinal cell layer. However, there is no direct evidence for this regulatory process. The first goal of this work was to establish the germ-free mice intestinal glycosylation baseline using a histochemical approach and a panel of ten lectins with defined glycan specificities to tissue sections prepared from various cellular compartments of the small and large intestine. Using this baseline, we have studied the contribution of the gut microflora on the carbohydrate composition of glycoconjugates of intestinal cells by comparing the germ-free and conventional mice glycosylation patterns. Analysis of the germ-free mice intestinal glycosylation baseline revealed that the expression of glycans depends on the proximodistal gradient (small to large intestine) and on the cell lineage (absorptive, goblet, crypt, and Paneth cells), indicating that mice are able to create and maintain a strict topological and cell lineage-specific regulation of glycosyltransferase expression. By comparing germ-free and conventional mice, we find that the gut microflora specifically modulates the gut glycosylation pattern, quantitatively as well as qualitatively by changing the cellular and subcellular distribution of glycans. This is the first report in mice to directly demonstrate the critical contribution of microflora to intestinal glycosylation, a key characteristic of the gut.
MeSH term(s)	Animals ; Carbohydrate Metabolism ; Carbohydrates/analysis ; Enterocytes/chemistry ; Enterocytes/ultrastructure ; Glycosylation ; Goblet Cells/chemistry ; Goblet Cells/ultrastructure ; Golgi Apparatus/chemistry ; Intestinal Mucosa/chemistry ; Intestinal Mucosa/cytology ; Intestinal Mucosa/microbiology ; Intestine, Large/chemistry ; Intestine, Large/cytology ; Intestine, Large/microbiology ; Intestine, Small/chemistry ; Intestine, Small/cytology ; Intestine, Small/microbiology ; Lectins ; Mice ; Microvilli/chemistry ; Staining and Labeling
Chemical Substances	Carbohydrates ; Lectins
Language	English
Publishing date	2002-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1222930-1
ISSN	1432-119X ; 0948-6143 ; 0301-5564
ISSN (online)	1432-119X
ISSN	0948-6143 ; 0301-5564
DOI	10.1007/s00418-002-0432-0
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