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| 2. |
- Jatta, Ken, et al.
(författare)
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Lipopolysaccharide-induced cytokine and chemokine expression in human carotid lesions
- 2005
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 42:3, s. 266-271
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Tidskriftsartikel (refereegranskat)abstract
- The release of cytokines and chemokines from activated immune-competent cells plays a crucial role in determining the pathology of the atherogenic progress. We investigated the effect of bacterial lipopolysaccharide (LPS) on cytokine/chemokine expression in carotid lesions and normal renal arteries. The lesions or renal arteries were incubated for 6 h at 37 degrees C in serum-free media treated with or without LPS. After LPS treatment, increased protein levels of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and MCP-1 were observed in the culture medium from the lesions measured with cytometric bead array. We were able to detect the induction of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and MCP-1 mRNA in the lesions after stimulation with LPS using real-time PCR. In renal arteries, LPS also induces mRNA expression of all chemokines and cytokines investigated with the exception of IL-6. However, LPS induces significantly higher levels of TNF-alpha, IL-1beta and IL-10 mRNA in lesions compared to renal arteries. The results suggest that infectious agents are capable of enhancing the production of cytokines/chemokines in an already ongoing inflammatory process such as in atherosclerosis, and that low levels of circulating LPS may affect the levels of pro-inflammatory cytokines much more in atherosclerotic vessels than in normal vessels and may contribute to the development of the atherosclerotic lesion.
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| 3. |
- Olofsson, Peder S., et al.
(författare)
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CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice
- 2008
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Ingår i: Circulation. - Baltimore, Md. : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 117:10, s. 1292-1301
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Tidskriftsartikel (refereegranskat)abstract
- Background— Atherosclerosis is a multifactorial disease in which inflammatory processes play an important role. Inflammation underlies lesion evolution at all stages, from establishment to plaque rupture and thrombosis. Costimulatory molecules of the tumor necrosis factor superfamily such as CD40/CD40L and OX40/OX40L have been implicated in atherosclerosis. Methods and Results— This study shows that the tumor necrosis factor superfamily members CD137 and CD137 ligand (CD137L), which play a major role in several autoimmune diseases, may constitute a pathogenic pair in atherogenesis. We detected CD137 protein in human atherosclerotic lesions not only on T cells but also on endothelial cells and showed that CD137 in cultured endothelial cells and smooth muscle cells was induced by proinflammatory cytokines implicated in atherosclerosis. Activation of CD137 by CD137L induced adhesion molecule expression on endothelial cells and reduced smooth muscle cell proliferation. In addition, treatment of atherosclerosis-prone apolipoprotein E–deficient mice with a CD137 agonist caused increased inflammation. T-cell infiltration, mainly of CD8+ cells, and expression of the murine major histocompatibility complex class II molecule I-Ab increased significantly in atherosclerotic lesions, as did the aortic expression of proinflammatory cytokines. Conclusions— Taken together, these observations suggest that CD137-CD137L interactions in the vasculature may contribute to the progression of atherosclerosis via augmented leukocyte recruitment, increased inflammation, and development of a more disease-prone phenotype.
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| 4. |
- Olofsson, Peder, et al.
(författare)
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The antiviral cytomegalovirus inducible gene 5/viperin is expressed in atherosclerosis and regulated by proinflammatory agents
- 2005
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 25:7, s. 113-116
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Inflammatory processes play an important role in atherosclerosis, and increasing evidence implies that microbial pathogens and proinflammatory cytokines are involved in the development and activation of atherosclerotic lesions. To find new inflammatory genes, we explored the vascular transcriptional response to an activator of innate immunity bacterial lipopolysaccharides (LPSs).METHODS AND RESULTS:Gene arrays identified the cytomegalovirus-inducible gene 5 (cig5)/viperin among the genes most potently induced by LPS in human vascular biopsies. Viperin was expressed by endothelial cells in atherosclerotic arteries and significantly elevated in atherosclerotic compared with normal arteries. In culture, cytomegalovirus infection, interferon-gamma, and LPS induced viperin expression.CONCLUSIONS:Viperin is expressed in atherosclerosis and induced in vascular cells by inflammatory stimuli and cytomegalovirus infection. The putative functions of viperin in atherosclerosis may relate to disease-associated microbes.
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| 5. |
- Sirsjö, Allan
(författare)
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Acute skeletal muscle ischemia and reperfusion in the rat : The role of leukocytes and the effect of hyperbaric oxygen on microcirculation and metabolism during reperfusion
- 1994
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Much experimental work in recent years seems to indicate that reperfusion after long periods of ischemia can damage tissue. Suggested factors of importance are accumulation of polymorphonuclear leukocytes (PMNs) and production of reactive oxygen metabolites (ROMs). In these experimental studies, a rat hindlimb tourniquet model was used to investi-gate the accumulation and the role of PMN's and the effect of hyperbaric oxygen (HBO) on post-ischemic skeletal muscle dysfunction. HBO was used, because post-ischemic oxygen delivery is said to be associated with production of ROM's. The activity of the PMN-specific enzyme myelo-peroxidase (MPO) in muscle homogenates was used as an index for the presence of PMNs.After 3 hours of ischemia, reperfusion periods longer than 1 hour were required to observe a significantly increased MPO activity com-pared to non-ischemic control. There was a significant increase in MPO activity after 5 hours of reperfusion, which was further increased up to 24 hours of reperfusion and had returned to control levels after 72 hours ofreperfusion. There was no significant correlation between MPO activity, edema and blood flow seen during reperfusion following 3 or 4 hours of ischemia, with one exception. Mter 4 hours of ischemia and I hour of reperfusion there was a significant correlation between the MPO activity and the extent of edema.Prevention of post-ischemic muscle accumulation of PMNs by pretreatment with antineutrophil serum did not affect the microvascular dysfunction (reduced blood flow and edema formation) and the metabolic restitution after 18 hours of reperfusion following 4 hours of ischemia.HBO treatment during the first hour of reperfusion after 3 hours of ischemia significantly increased the levels of ATP, PCr and glutathione and reduced the edema seen after 5 hours reperfusion. After 4 hours of ischemia HBO treatment failed to improve the levels of ATP, PCr and glutathione and affect the edema but improved the blood flow seen after 5 hours of reperfusion.It is concluded from these results that in this model, damage by PMN's seems minor during reperfusion. The improvement seen with HBO indicate that there is a prevailing or lingering effect of residual hypoxia in the post-ischemic muscle tissue that can be attenuated by HBO.
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| 6. |
- Sirsjö, Allan, et al.
(författare)
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Deficiency of nitric oxide synthase 2 results in increased neointima formation in a mouse model of vascular injury
- 2003
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Ingår i: Journal of Cardiovascular Pharmacology. - : Lippincott Williams & Wilkins. - 0160-2446 .- 1533-4023. ; 41:6, s. 897-902
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Tidskriftsartikel (refereegranskat)abstract
- Restenosis frequently occurs after arterial interventions. The inducible form of nitric oxide synthase (NOS2) may both promote and inhibit neointima formation. This study investigated the role of NOS2 for neointima formation in a mouse model of carotid artery injury. The common carotid artery was ligated in anesthetized mice. Homozygous NOS2 knockout mice were compared with wild-type B6/129 mice or wild-type mice treated with the pharmacologic NOS2 inhibitor aminoguanidine given orally daily after ligation (n = 6-8 in each group). Vessels were harvested for quantification of lesion size 4 weeks later, or serially after ligation for tissue analysis. mRNA for NOS2 increased 1-4 days after ligation of the carotid artery. Cell proliferation could be visualized with an antibody against proliferating cell nuclear antigen. An intimal smooth muscle cell layer, confirmed by an alpha-actin antibody, was observed in the lumen 4 weeks after injury. Inhibition of NOS2 by either pharmacologic or genetic approaches tended to increase the area of intima formation (P = 0.13 or P less than 0.05, respectively) and increased the intima/media ratio (P = 0.14 and P less than 0.01, respectively). Inhibition of NOS2 by two different approaches increased neointima formation in a mouse model of mechanical vessel injury, indicating that the NOS2 expressed in the injured vessel wall is beneficial.
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| 7. |
- Uggla, Bertil, 1962-, et al.
(författare)
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BCRP mRNA expression v. clinical outcome in 40 adult AML patients
- 2005
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Ingår i: Leukemia research. - Amsterdam : Elsevier. - 0145-2126 .- 1873-5835. ; 29:2, s. 141-146
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Tidskriftsartikel (refereegranskat)abstract
- Efflux pumps are considered being mechanisms behind drug resistance in acute myeloid leukaemia (AML). A recently described efflux pump, breast cancer resistance protein (BCRP), can be expressed in AML, but its clinical importance is uncertain. In this study BCRP mRNA expression was determined in samples from 40 AML patients by real-time RT-PCR. The expression varied from negative to 76 times that of control cells. There was no difference in BCRP mRNA expression between patients responding to induction treatment and non-responders. However, in the group of responders, the 14 patients with the highest expression had significantly shorter overall survival (mean 38 months, SEM 15 months) than the 14 patients with the lowest (74 months, SEM 16 months) (P = 0.047). This suggests a possible role of BCRP in drug resistance in AML.
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| 8. |
- Wuttge, Dirk M., et al.
(författare)
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CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor expressed in atherosclerotic lesions
- 2004
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 24:4, s. 750-755
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-gamma (IFN-gamma)-cytokine abundant in atherosclerotic lesions. METHODS AND RESULTS: CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E-deficient mice. In vitro IFN-gamma induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be blocked by peptide antibodies against CXCL16. In vivo IFN-gamma induced CXCL16 expression in murine atherosclerotic lesions. CONCLUSIONS: We demonstrate a novel role of IFN-gamma in foam cell formation through upregulation of CXCL16/SR-PSOX. CXCR6 expression in the plaque confirms the presence of cells able to respond to CXCL16. Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion.
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| 9. |
- Wågsäter, Dick, et al.
(författare)
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Analysis of MICA gene transcripts in human rectal cancers
- 2003
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 23:3B, s. 2525-2529
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Wågsäter, Dick, et al.
(författare)
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Down-regulation of ID2 by all-trans retinoic acid in monocytic leukemia cells (THP-1)
- 2003
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : BioMed Central (BMC). - 1756-9966. ; 22:3, s. 471-475
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Tidskriftsartikel (refereegranskat)abstract
- Accumulated evidence supports that both Id helix-loop-helix proteins and derivatives of vitamin A, retinoids, play a pivotal role in the regulation of cell growth and differentiation. We analyzed the effects of all-trans retinoic acid (atRA) on the gene and protein expression of Id2 in THP-1 cells and found a suppression of the levels of Id2. The down-regulation was abolished towards a constitutively expressed level of Id2 mRNA. The decreased level of Id2 was associated with growth suppression and does support the prevalent conception of the action of Id2 as a stimulator of cell growth.
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