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Wahlström, O., Risto, O., Kalén, A., Linder, C., Ansell, A., Söderström, M. & Magnusson, P. (2011). Acidic preparations of lysed platelets up-regulate proliferative and vascular genes, and the TGFBR pathway in osteoblast-like cells in BONE, vol 48, issue , pp S118-S118. In: BONE (pp. S118-S118). Elsevier Science B.V., Amsterdam., 48.
Open this publication in new window or tab >>Acidic preparations of lysed platelets up-regulate proliferative and vascular genes, and the TGFBR pathway in osteoblast-like cells in BONE, vol 48, issue , pp S118-S118
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2011 (English)In: BONE, Elsevier Science B.V., Amsterdam. , 2011, Vol. 48, S118-S118 p.Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68230 (URN)10.1016/j.bone.2011.03.215 (DOI)000289879800194 ()
Available from: 2011-05-13 Created: 2011-05-13 Last updated: 2013-10-23
Wahlström, O., Linder, C., Ansell, A., Kalén, A., Söderström, M. & Magnusson, P. (2011). Acidic preparations of lysed platelets upregulate proliferative pathways in osteoblast-like cells as demonstrated by genome-wide microarray analysis. Platelets, 22(6), 452-460.
Open this publication in new window or tab >>Acidic preparations of lysed platelets upregulate proliferative pathways in osteoblast-like cells as demonstrated by genome-wide microarray analysis
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2011 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 22, no 6, 452-460 p.Article in journal (Refereed) Published
Abstract [en]

latelets contain numerous growth factors essential for wound and fracture healing. We investigated the gene expression in human osteoblast-like cells stimulated with lysed platelets prepared in acidic, neutral, or alkaline buffers. Lysed platelets prepared in buffers at pH 5.4, 7.4, and 7.9, were added after neutralization to hFOB 1.19 cells. Genome-wide microarray analysis was performed using the Affymetrix GeneChip 7G Scanner. Biometric, cluster, and pathway analyses were performed with GeneSpring GX. Biometric analyses demonstrated that 53 genes were differentially regulated (p andlt;= 0.005, andgt;= 2-fold increase). Pathway analysis revealed 10 significant pathways of which eight are common ones regulating bone formation and cancer growth. Eleven genes were selected for quantitative real-time polymerase chain reaction (PCR) based on the microarray analysis of the lysed platelets prepared in the pH 5.4 experiments. In conclusion, acidic preparations of lysed platelet concentrates release factors essential for cell proliferation and particularly cell metabolism under hypoxic conditions. The genetic response from these factors was dominated by genes associated with the same pathways observed in bone formation and cancer growth. Activation of TGF-beta in the acidic preparation could be a stimulatory key factor of cell proliferation. These results support the hypothesis that acidification of platelets modifies the stimulatory response of mesenchymal cells in vitro, which is analogous with the observed milieu of a low pH present in wound and fracture sites, as well as in growing tumors.

Place, publisher, year, edition, pages
Informa Healthcare, 2011
Keyword
Cell proliferation, gene expression, hypoxia, platelets, TGFBR pathway
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70115 (URN)10.3109/09537104.2011.565432 (DOI)000293600300008 ()
Note

Original Publication: Ola Wahlström, Cecilia Linder, Anna Ansell, Anders Kalén, Mats Söderström and Per Magnusson, Acidic preparations of lysed platelets upregulate proliferative pathways in osteoblast-like cells as demonstrated by genome-wide microarray analysis, 2011, Platelets, (22), 6, 452-460. http://dx.doi.org/10.3109/09537104.2011.565432 Copyright: Informa Healthcare http://informahealthcare.com/

Available from: 2011-08-19 Created: 2011-08-19 Last updated: 2017-12-08
Strid, T., Svartz, J., Franck, N., Hallin, E., Ingelsson, B., Söderström, M. & Hammarström, S. (2009). Distinct parts of leukotriene C-4 synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein. Biochemical and Biophysical Research Communications - BBRC, 381(4), 518-522.
Open this publication in new window or tab >>Distinct parts of leukotriene C-4 synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein
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2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 381, no 4, 518-522 p.Article in journal (Refereed) Published
Abstract [en]

Leukotriene C-4 is a potent inflammatory mediator formed from arachidonic acid and glutathione. 5-Lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP) and leukotriene C-4 synthase (LTC4S) participate in its biosynthesis. We report evidence that LTC4S interacts in vitro with both FLAP and 5-LO and that these interactions involve distinct parts of LTC4S. FLAP bound to the N-terminal part/first hydrophobic region of LTC4S. This part did not bind 5-LO which bound to the second hydrophilic loop of LTC4S. Fluorescent FLAP- and LTC4S-fusion proteins co-localized at the nuclear envelope. Furthermore, GFP-FLAP and GFP-LTC4S co-localized with a fluorescent ER marker. In testing HEK293/T or COS-7 cells GFP-5-LO was found mainly in the nuclear matrix. Upon stimulation with calcium ionophore, GFP-5-LO translocated to the nuclear envelope allowing it to interact with FLAP and LTC4S. Direct interaction of 5-LO and LTC4S in ionophore-stimulated (but not un-stimulated) cells was demonstrated by BRET using GFP-5-LO and Rluc-LTC4S.

Keyword
BRET, Confocal fluorescence microscopy, Eicosanoids, Fusion proteins, GFP, GST pull-down assay, Nuclear envelope
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17904 (URN)10.1016/j.bbrc.2009.02.074 (DOI)000264929400013 ()
Note

Original Publication: Tobias Strid, Jesper Svartz, Niclas Franck, Elisabeth Hallin, Björn Ingelsson, Mats Söderström and Sven Hammarström, Distinct parts of leukotriene C-4 synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein, 2009, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, (381), 4, 518-522. http://dx.doi.org/10.1016/j.bbrc.2009.02.074 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/

Available from: 2009-04-30 Created: 2009-04-24 Last updated: 2017-12-13Bibliographically approved
Strid, T., Karlsson, C., Söderström, M., Zhang, J., Qian, H., Sigvardsson, M. & Hammarström, S. (2009). Fetal hepatic expression of 5-lipoxygenase activating protein is confined to colonizing hematopoietic cells. Biochemical and Biophysical Research Communications - BBRC, 383(3), 336-339.
Open this publication in new window or tab >>Fetal hepatic expression of 5-lipoxygenase activating protein is confined to colonizing hematopoietic cells
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2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 383, no 3, 336-339 p.Article in journal (Refereed) Published
Abstract [en]

Leukotriene C-4 is a potent inflammatory mediator formed from arachidonic acid and glutathione. 5-Lipoxygenase (540), 5-lipoxygenase activating protein (FLAP) and leukotriene C-4 synthase (LTC4S) participate in its biosynthesis. We report evidence from in situ hybridization experiments that FLAP mRNA is abundantly expressed in fetal mouse liver from e11.5 until delivery. In contrast very little or no FLAP mRNA was detected in adult liver. The fetal expression in liver was not uniform but occurred in patches. Cells from e15.5 livers were fractionated by fluorescence activated cell sorting into hepatocytes and other CD45(-) cells and CD45(+) hematopoietic cells. The latter were further separated into immature (Lin(-)) and mature (Lin(+)) cells and analyzed for FLAP mRNA content by quantitative RT-PCR. FLAP mRNA expression was confined to CD45(+) cells and the mature cells had approximately 4-fold higher FLAP mRNA levels compared to the immature cells.

Keyword
Embryonic development, Fluorescence-activated cell sorting, In situ hybridization, Leukotrienes, 5-Lipoxygenase activating protein, Liver, Hematopoietic cells
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18568 (URN)10.1016/j.bbrc.2009.04.007 (DOI)000265966800012 ()
Available from: 2009-06-01 Created: 2009-06-01 Last updated: 2017-12-13Bibliographically approved
Strid, T., Söderström, M. & Hammarström, S. (2008). Leukotriene C4 synthase promoter driven expression of GFP reveals cell specificity. Biochemical and Biophysical Research Communications - BBRC, 366(1), 80-85.
Open this publication in new window or tab >>Leukotriene C4 synthase promoter driven expression of GFP reveals cell specificity
2008 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 366, no 1, 80-85 p.Article in journal (Refereed) Published
Abstract [en]

Leukotriene C4 synthase is a key enzyme in leukotriene biosynthesis. Its gene has been cloned and mapped to mouse chromosome 11. Expression occurs in cells of myeloid origin and also in the choroid plexus, the hypothalamus and the medial eminence of mouse brain. In this study a vector that expresses enhanced green fluorescent protein (eGFP) under the control of the mouse leukotriene C4 synthase promoter was constructed and used to study promoter activity in different cell lines. Specific eGFP expression was observed in human monocytic leukemia (THP-1) and rat basophilic leukemia (RBL-1) myeloid cells which both express leukotriene C4 synthase, but not in human embryonic kidney (HEK293/T) epithelial cells which do not express this enzyme. In the myeloid cells, but not in the epithelial cells, we observed that the leukotriene C4 synthase promoter activity was stimulated by 12-O-tetradecanoylphorbol-13-acetate and all-trans-retinoic acid. In contrast dimethyl sulfoxide did not affect promoter activity. © 2007 Elsevier Inc. All rights reserved.

Keyword
Leukotriene; Leukotriene C4 synthase; Expression; GFP; TPA; Promoter; Retinoic acid; DMSO
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42196 (URN)10.1016/j.bbrc.2007.11.097 (DOI)000252392400013 ()61334 (Local ID)61334 (Archive number)61334 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
Davidsson, A., Söderström, M., Naidu Sjöswärd, K. & Schmekel, B. (2007). Chlorine in Breath Condensate: A Measure of Airway Affection in Pollinosis?. Respiration, 74(2), 184-191.
Open this publication in new window or tab >>Chlorine in Breath Condensate: A Measure of Airway Affection in Pollinosis?
2007 (English)In: Respiration, ISSN 0025-7931, E-ISSN 1423-0356, Vol. 74, no 2, 184-191 p.Article in journal (Refereed) Published
Abstract [en]

Background: Infiltration of inflammatory cells in bronchial mucosa and glandular hypersecretion are hallmarks of asthma. It has been postulated that exhaled breath condensate (EBC) mirrors events in epithelial lining fluid of airways, such as presence of local inflammation as well as glandular hypersecretion. It is also well known that eosinophil cationic protein (ECP) and cysteinyl-leukotrienes (cys-LT) are released by circulating inflammatory cells when triggered by antigen stimulation in asthma patients.

Objectives: The aim of this study was to evaluate whether chlorine and/or cys-LT in EBC would reflect changes of exposure of airborne pollen in patients with asthma.

Methods: EBC and serum were collected from 23 patients with allergic asthma during a pollen season and repeated 5 months later during a period with no aeroallergens. Chlorine was measured by means of a sensitive coulometric technique and cys-LT by an EIA technique. Serum ECP was measured and lung function tests were performed and symptoms noted during both occasions.

Results: Significantly higher concentrations of chlorine in EBC (p = 0.007) and ECP in serum (p = 0.003) were found during the pollen season compared to post-season. Chlorine levels tended to be higher in patients who reported of chest symptoms compared to those who denied symptoms during the pollen season (p = 0.06). Areas under the receiver-operated characteristic curves (AUCROC) were compared and similar discriminative power to identify exacerbations of asthma was recorded by chlorine in EBC (range 0.67-0.78) and ECP in serum (range 0.64-0.78).

Conclusion: It is concluded that chlorine in EBC and ECP in serum decreased significantly post-season, and this is suggested to mirror the decrement in airborne antigen. It is furthermore proposed that chlorine in EBC and ECP in serum tend to have a similar capacity to identify seasonal variations in airborne pollen in patients with asthma.

Place, publisher, year, edition, pages
Karger, 2007
Keyword
Pollen season, Allergic asthma, Exhaled breath condensate, Serum eosinophil cationic protein, Chlorine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16291 (URN)10.1159/000091300 (DOI)000244565600010 ()
Available from: 2009-01-13 Created: 2009-01-13 Last updated: 2017-12-14Bibliographically approved
Sauma, L., Franck, N., Paulsson, J. F., Westermark, G. ., Kjølhede, P., Strålfors, P., . . . Nyström, F. H. (2007). Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes. Diabetologia, 50(1), 195-201.
Open this publication in new window or tab >>Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes
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2007 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 1, 195-201 p.Article in journal (Refereed) Published
Abstract [en]

AIMS/HYPOTHESIS: The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse.

MATERIALS AND METHODS: We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light. RESULTS: We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n = 23). The activity was also 6.2-fold higher in subcutaneous than in intra-abdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 micromol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells.

CONCLUSIONS/INTERPRETATION: We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

Keyword
x-ray, vibrational, spectrum, Hartree-Fock, static exchange, Franck-Condon
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18462 (URN)10.1007/s00125-006-0515-x (DOI)000243188000026 ()17106695 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved
Svensson, A.-C. B., Bengtsson, T., Grenegård, M., Söderström, M. & Lindström, E. G. (2007). Platelet fragments, like platelets, induce airway smooth muscle cell proliferation through mechanisms dependent on ros and 5-lox. Paper presented at EAS Helsinki. .
Open this publication in new window or tab >>Platelet fragments, like platelets, induce airway smooth muscle cell proliferation through mechanisms dependent on ros and 5-lox
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2007 (English)Conference paper, Published paper (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69418 (URN)
Conference
EAS Helsinki
Available from: 2011-06-27 Created: 2011-06-27 Last updated: 2013-10-23
Söderberg, A., Barral, A.-M., Söderström, M., Sander, B. & Rosén, A. (2007). Redox-signaling transmitted in trans to neighboring cells by melanoma-derived TNF-containing exosomes. Free Radical Biology and Medicine, 43(1), 90-99.
Open this publication in new window or tab >>Redox-signaling transmitted in trans to neighboring cells by melanoma-derived TNF-containing exosomes
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2007 (English)In: Free Radical Biology and Medicine, ISSN 0891-5849, Vol. 43, no 1, 90-99 p.Article in journal (Refereed) Published
Abstract [en]

Hydrogen peroxide is known to be involved in redox signaling pathways that regulate normal processes and disease progression, including cytokine signaling, oxidative stress, and cancer. In studies on immune surveillance against cancer, hydrogen peroxide was found to disrupt cytotoxic T-cell function, thus contributing to tumor escape. In this study, secretion of TNF-containing vesicles of rab9+ endosomal origin, termed exosomes, was investigated using GFP-TNF constructs. We observed a polarized intracellular trafficking and apical secretion of TNF-positive nanovesicles. Cell-to-cell transfer of TNF was observed in exosomes in real-time microscopy, occurring separate from the melanin/melanosome compartment. Exosomes were prepared by ultracentrifugation or immunoisolation on anti-β2-microglobulin magnetic beads. TNF as well as TNF receptors 1 and 2 were present in the exosomes as determined by Western blot, flow cytometry, and deconvolution microscopy. The functional significance of melanoma-derived exosomes was established by their signaling competence with ability to generate significantly higher ROS levels in T cells compared with sham exosomes (P = 0.0006). In conclusion, we report here, for the first time, that TNF is found in tumor cell-derived exosomes and that these exosomes transmit redox signaling in trans to neighboring cells. The results are of importance for a better understanding of tumor escape mechanisms.

Keyword
TNF, Exosomes, Melanoma, Hydrogen peroxide, Redox signaling, Tumor escape mechanisms
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13716 (URN)10.1016/j.freeradbiomed.2007.03.026 (DOI)000247395000011 ()
Available from: 2002-01-11 Created: 2002-01-11 Last updated: 2017-09-22
Svensson Holm, A.-C., Berg, C., Herbertsson, H., Söderström, M., Hammarström, S., Lindström, E. & Bengtsson, T. (2006). 5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation. Paper presented at Kardiovaskulära vårmötet, Linköping. .
Open this publication in new window or tab >>5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation
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2006 (English)Conference paper, Published paper (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69447 (URN)
Conference
Kardiovaskulära vårmötet, Linköping
Available from: 2011-06-28 Created: 2011-06-28 Last updated: 2013-10-23
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3927-4394

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