| 51. |
- Kulseth, Mari Ann, et al.
(författare)
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Serglycin expression during differentiation of U937-1 cells
- 1998
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Ingår i: Glycobiology. - 0959-6658 .- 1460-2423. ; 8:8, s. 747-753
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Tidskriftsartikel (refereegranskat)abstract
- Serglycin is the major proteoglycan in most hematopoietic cells, including monocytes and macrophages. The monoblastic cell line U937-1 was used to study the expression of serglycin during proliferation and differentiation. In unstimulated proliferating U937-1 cells serglycin mRNA is nonconstitutively expressed. The level of serglycin mRNA was found to correlate with the synthesis of chondroitin sulfate proteoglycan (CSPG). The U937-1 cells were induced to differentiate into different types of macrophage-like cells by exposing the cells to PMA, RA, or VitD3. These inducers of differentiation affected the expression of serglycin mRNA in three different ways. The initial upregulation seen in the normally proliferating cells was not observed in PMA treated cells. In contrast, RA increased the initial upregulation, giving a reproducible six times increase in serglycin mRNA level from 4 to 24 h of incubation, compared to a four times increase in the control cells. VitD3 had no effect on the expression of serglycin mRNA. The incorporation of (35S)sulfate into CSPG decreased approximately 50% in all three differentiated cell types. Further, the (35S)CSPGs expressed were of larger size in PMA treated cells than controls, but smaller after RA treatment. This was due to the expression of CSPGs, with CS-chains of 25 and 5 kDa in PMA and RA treated cells, respectively, compared to 11 kDa in the controls. VitD3 had no significant effect on the size of CSPG produced. PMA treated cells secreted 75% of the (35S)PGs expressed, but the major portion was retained in cells treated with VitD3 or RA. The differences seen in serglycin mRNA levels, the macromolecular properties of serglycin and in the PG secretion patterns, suggest that serglycin may have different functions in different types of macrophages.
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| 52. |
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| 53. |
- Kårehed, Karin, et al.
(författare)
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IFN-gamma-induced upregulation of Fc gamma-receptor-I during activation of monocytic cells requires the PKR and NF kappa B pathways
- 2007
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 44:4, s. 615-624
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Tidskriftsartikel (refereegranskat)abstract
- Interferon (IFN)-gamma is a potent activator of macrophages, increasing the cells capacity to perform specific functions during inflammation and immune response. In this report we use IFN-gamma-induced upregulation of the high affinity receptor for IgG (Fc gamma RI/CD64) in the human monocytic cell line U-937 as a model for monocytic activation. We show that upregulation of Fc gamma RI is dependent on signals mediated by the dsRNA-dependent kinase PKR, and the transcription factor NF kappa B. silencing of PKR expression by siRNA or inhibition of PKR by 2-aminopurine (2-AP) potently blocks the IFN-gamma-induced transcriptional activation of the Fc gamma RI promoter. We find that the serine 727 phosphorylation of Stat1, required for full IFN-gamma-induced Fc gamma RI promoter activity, is dependent on PKR. We further show that IFN-gamma induction of Fc gamma RI upregulation is dependent on the NF kappa B pathway, as evidenced by inhibition of NF kappa B using a phosphorylation defective I kappa B alpha (S32A/S36A) mutant, or inhibiting the IKB-kinase (IKK) by treatment with BMS345541. Our results suggest that IFN-gamma-induced increase of Fc gamma RI expression requires the integration of two signalling events: PKR-dependent Stat1 serine 727 phosphorylation, and activation of NF kappa B.
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| 54. |
- Kårehed, Karin, 1972-
(författare)
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Signal Transduction in Malignant Cells – Transformation, Activation and Differentiation
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- All aspects of cell life are regulated by signal transduction mechanisms. This thesis describes the regulatory roles of a few key signal transduction molecules involved in three major biological responses. The studied pathways include platelet derived growth factor (PDGF)-BB induced transformation of murine fibroblasts, interferon (IFN)-γ stimulated monocyte activation and all-trans retinoic acid (ATRA) induced myeloid differentiation.We found that intact phosphoinositide 3OH-kinase (PI3K) activity is essential in the signaling pathway that leads to the morphological alterations and migration pattern characteristic of PDGF-BB transformed NIH/sis and NIH/COL1A1 fibroblasts. Furthermore, our data indicated that the small Rho-GTPase, Rac1 is the predominant mediator of these signals downstream of PI3K.The study of the IFN-γ induced activation of monocytic U-937 cells showed that upregulation of the high affinity receptor for IgG (FcγRI) is dependent on the coordination of several regulatory events: the PKR-mediated serine 727 phosphorylation of Stat1, the expression of the hematopoietic lineage specific transcription factor PU.I, and the activation of the NFκB pathway.ATRA-induced differentiation and cell cycle arrest are impaired in U-937 sublines expressing phosphorylation deficient Stat1 (Stat1Y701F and Stat1S727A). The findings in paper III indicated that the expression pattern of the myeloid specific transcription factors Stat2, ICSBP and c/EBPε was altered in the sublines and that intact Stat1 activation is critical for maintaining the balance of the transcriptional network during ATRA induced terminal differentiation.Finally, ATRA-induced differentiation and growth arrest were blocked by treatment with the IKKα/β inhibitor BMS345541 or by ectopic expression of the NFκB super repressor IκBα (S32A/S36A). The fact that IκB(AA) sublines differentiated normally in response to vitamin D3, showed that NFκB inhibition specifically affected ATRA induced responses. Notably we suggest that the activity of the NFκB pathway may interfere with the differentiation process via a direct effect on the RAR/RXR mediated transcription.
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| 55. |
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| 56. |
- Larsson, Erik, et al.
(författare)
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Expression of the endogenous retrovirus ERV3 (HERV-R) during induced monocytic differentiation in the U-937 cell line
- 1996
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 67:3, s. 451-456
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Tidskriftsartikel (refereegranskat)abstract
- ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. LTR-env-gene-spliced mRNA of 9 and 3.5 Kb is widely expressed in human tissues and cells, but gag-pol mRNA has not been found. Further, the env gp70 gene contains an open reading frame throughout its length and its expression has recently been detected as a full-length protein. The highest expression of ERV3 detected so far is in placenta and the lowest in cytotrophoblasts and choriocarcinoma cell lines. In this report we have studied ERV3 mRNA and protein expression in the human monoblastic cell line U-937 during differentiation into monocytes/macrophages. Differentiation of U-937 cells was induced by 1,25a-dihydroxyvitamin D3 (vitD3), retinoic acid (RA), gamma interferon (IFN-gamma) and phorbol-myristate-acetate (PMA-TPA). The expression of ERV3 env mRNA was found to be differentiation-associated, with high expression detected in the late stages of monocytic development. Using TPA, the expression of ERV3 env was detected as 9- and 3.5-kb transcripts by Northern blotting, as mRNA by in situ hybridization and as a cytoplasmic 65-kDa protein by immunofluorescence and Western blots. Low levels of basal expression were found, with up-regulation of both message and protein at 24 to 48 hr after addition of TPA. Induction with vitD3, IFN-gamma and RA produced higher levels of mRNA at earlier time points. It is concluded that the U-937 cell line represents an excellent model system for further studies to study the relationship between ERV3 expression and cellular differentiation.
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| 57. |
- Larsson, Erik, et al.
(författare)
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Tissue and differentiation specific expression of the endogenous retrovirus ERV3 (HERV-R) in normal human tissues and during induced monocytic differentiation in the U-937 cell line
- 1997
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Ingår i: Leukemia. - 0887-6924 .- 1476-5551. ; 11:Suppl. 3, s. 142-4
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Tidskriftsartikel (refereegranskat)abstract
- ERV3 (HERV-R) is a complete, single copy human endogenous retrovirus located on the long arm of chromosome 7. The open reading frame in its envelope gene has been conserved during evolution but the gag and pol genes contain in-frame termination codons. To find a suitable experimental model system for analysis of the functions of the ERV3 genome, an extensive screening study of different normal and neoplastic human tissues was performed. Most tissues express low levels of the ERV3 env mRNA although high expression levels are observed in placenta, sebaceous glands, adrenals, testis, bronchial, epithelium and the monocytic cell line U-937. In U-937 cells the ERV3 env expression varied in a manner related to the differentiation status of the cells; being highest in the terminally differentiated non proliferating cells. U-937 cells can be induced to differentiate from the monoblastic to the mature monocyte/macrophage stage upon stimulation by several substances such as phorbolesters (TPA), Vitamin D3, Retinoic Acid (RA) and combinations of some cytokines. We conclude that the ERV3 locus is expressed in a tissue and differentiation specific way and that the U-937 cell line is a suitable model system to further analyze the proposed functions of ERVs such as immunomodulation, cell fusion and protection against exogenous retroviral infections.
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| 58. |
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| 59. |
- Larsson, Maria, et al.
(författare)
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Bad odors stick better than good ones : Olfactory qualities and odor recognition
- 2009
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Ingår i: Experimental psychology (Göttingen). - : Hogrefe & Huber Publishers. - 1618-3169 .- 2190-5142. ; 56:6, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- The influences of perceived odor qualities on the retention of olfactory information across the adult lifespan were examined. Young (19–36 years), young-old (60–74 years), and old (75–91 years) adults (n = 202) rated a set of unfamiliar odors across a series of perceptual dimensions (i.e., pleasantness, intensity, and irritability) at encoding. The overall results indicated that memory for unpleasant olfactory information was better than that for pleasant odors across the lifespan. Also, participants showed better retention for odors perceived with high intensity and irritability than for odors rated with low or medium scores. Interestingly, the old adults showed selective beneficial memory effects for odors rated as highly irritable. To the extent that perceptions of high irritability reflect an activation of the trigeminal sensory system, this finding suggests that older adults may use trigeminal components in odor information to compensate for age-related impairments in olfactory memory.
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| 60. |
- Larsson, Oscar, 1978-
(författare)
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The Governmentality of Meta-governance : Identifying Theoretical and Empirical Challenges of Network Governance in the Political Field of Security and Beyond
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Meta-governance recently emerged in the field of governance as a new approach which claims that its use enables modern states to overcome problems associated with network governance. This thesis shares the view that networks are an important feature of contemporary politics which must be taken seriously, but it also maintains that networks pose substantial analytical and political challenges. It proceeds to investigate the potential possibilities and problems associated with meta-governance on both theoretical and empirical levels.The theoretical discussion examines meta-governance in relation to governmentality, and it puts forward the claim that meta-governance may be understood as a specific type of neo-liberal governmentality. The meta-governance perspective regards networks as a complementary structure to traditional administration that can be utilized in the implementation and realization of public policy, but which also preserves the self-regulating and flexible character of networks. This generates a contradiction between the goals of public management and the character of networks that requires further investigation.The combination of the specific dynamics of the political field of security, the diminishing role of sovereign powers, the emergence of security networks, and the meta-governance stance adopted by the Swedish state constitutes a situation that should have been favorable for the successful employment of meta-governance. The empirical investigation of meta-governance is divided into two parts. The first part reviews the historical process involved and shows how the Swedish government and public authorities have adopted a meta-governance stance. The second analyzes the specific instruments and strategies that have been deployed in the governance of security communications and in the management of Sweden’s new security communications system which is an important aspect of security networks. The historical study together with the analysis of the meta-governance tools deployed reveals that the meta-governors neither reached the goals specified, nor fulfilled the overall purpose of successful security communications.I argue on the basis of the theoretical and empirical findings obtained in the present study that it is very difficult to successfully employ meta-governance in respect to security and crisis management, and that we have sound reasons to suspect that meta-governance will run into similar difficulties in other political fields as well. I conclude that meta-governance is a far more difficult practice than has been anticipated by existing theories and policy recommendations. Turning to meta-governance as a way to govern and control organizations may in fact lead to further fragmentation and distortion of public politics.
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