Kristin Larsen Sand

• Baysa, Anton; Maghazachi, Azzam; Sand, Kristin Larsen; Campesan, Marika; Zaglia, Tania & Mongillo, Marco [Show all 13 contributors for this article] (2022). Toll-like receptor 9 signaling after myocardial infarction: Role of p66ShcA adaptor protein. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 644, p. 70–78. doi: 10.1016/j.bbrc.2022.12.085. Full text in Research Archive Show summary

  During myocardial infarction, cellular debris is released, causing a sterile inflammation via pattern recognition receptors. These reactions amplify damage and promotes secondary heart failure. The pattern recognition receptor, Toll-like receptor 9 (TLR9) detects immunogenic fragments of endogenous DNA, inducing inflammation by NFκB. The p66ShcA adaptor protein plays an important role in both ischemic myocardial damage and immune responses. We hypothesized that p66ShcA adaptor protein promotes DNA-sensing signaling via the TLR9 pathway after myocardial infarction. TLR9 protein expression increased in cardiac tissue from patients with end-stage heart failure due to ischemic heart disease. Myocardial ischemia in mice in vivo induced gene expression of key TLR9 pathway proteins (MyD88 and Unc93b1). In this model, a functional link between TLR9 and p66ShcA was revealed as; (i) ischemia-induced upregulation of TLR9 protein was abrogated in myocardium of p66ShcA knockout mice; (ii) when p66ShcA was overexpressed in NFkB reporter cells stably expressing TLR9, NFkB-activation increased during stimulation with the TLR9 agonist CpG B; (iii) in cardiac fibroblasts, p66ShcA overexpression caused TLR9 upregulation. Co-immunoprecipitation showed that ShcA proteins and TLR9 may be found in the same protein complex, which was dissipated upon TLR9 stimulation in vivo. A proximity assay confirmed the co-localization of TLR9 and ShcA proteins. The systemic immune response after myocardial ischemia was dampened in p66ShcA knockout mice as interleukin-4, -17 and −22 expression in mononuclear cells isolated from spleens was reduced. In conclusion, p66ShcA adaptor may be an interaction partner and a regulator of the TLR9 pathway post-infarction.

• Rutkovskiy, Arkady; Olovyannikova, Maria; Siamansour, Tanja; Reine, Trine M.; Kolset, Svein Olav & Sand, Kristin Larsen [Show all 12 contributors for this article] (2019). Mechanical stress alters the expression of calcification-related genes in vascular interstitial and endothelial cells. Interactive Cardiovascular and Thoracic Surgery. ISSN 1569-9293. 28(5), p. 803–811. doi: 10.1093/icvts/ivy339. Full text in Research Archive
• Maghazachi, Azzam A; Sand, Kristin Larsen & Al-Jaderi, Zaidoon (2016). Glatiramer acetate, dimethyl fumarate, and monomethyl fumarate upregulate the expression of CCR10 on the surface of natural killer cells and enhance their chemotaxis and cytotoxicity. Frontiers in Immunology. 7. doi: 10.3389/fimmu.2016.00437. Full text in Research Archive Show summary

  In vitro harnessing of immune cells is the most important advance in the field of cancer immunotherapy. Results shown in the current paper may be used to harness natural killer (NK) cells in vitro. It is observed that drugs used to treat multiple sclerosis such as glatiramer acetate, dimethyl fumarate, and monomethyl fumarate upregulate the expression of chemokines receptor 10 (CCR10) on the surface of human IL-2-activated NK cells. This is corroborated with increased chemotaxis of these cells toward the concentration gradients of the ligands for CCR10, namely CCL27 and CCL28. It is also demonstrated that these three drugs enhance NK cell cytotoxicity against tumor target cells, an activity that is abrogated by prior incubation of the cells with anti-CCR10 antibody. Because CCL27 and CCL28 are secreted by selective tumor types such as malignant melanoma, squamous cell carcinomas, and colorectal cancer, respectively, it is hypothesized that activated NK cells may be harnessed in vitro with any of these drugs before utilizing them as a therapeutic modality for cancer.

• Vego, Heidi; Sand, Kristin Larsen; Høglund, Rune Alexander; Fallang, Lars-Egil; Gundersen, Glenn & Holmøy, Trygve [Show all 7 contributors for this article] (2014). Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CD107a. Cellular & Molecular Immunology. ISSN 1672-7681. 13(1), p. 57–64. doi: 10.1038/cmi.2014.114. Full text in Research Archive
• Bøyum, Arne; Forstrøm, Rune Johansen; Sefland, Iren; Sand, Kristin Larsen & Benestad, Haakon Breien (2014). Intricacies of redoxome function demonstrated with a simple in vitro chemiluminescence method, with special reference to vitamin B12 as antioxidant. Scandinavian Journal of Immunology. ISSN 0300-9475. 80(6), p. 390–397. doi: 10.1111/sji.12220. Full text in Research Archive
• Sand, Kristin Larsen; Flatebø, Torun; Andersen, Marian Berge & Maghazachi, Azzam (2013). Effects of exercise on leukocytosis and blood hemostasis in 800 healthy young females and males. World Journal of Experimental Medicine. 3(1), p. 11–20. Full text in Research Archive
• Aas, Vigdis; Sand, Kristin Larsen; Åsheim, Hans-Christian; Benestad, Haakon Breien & Iversen, Jens Gustav Heber (2013). C-Reactive Protein Triggers Calcium Signalling in Human Neutrophilic Granulocytes via FcγRIIa in an Allele-Specific Way. Scandinavian Journal of Immunology. ISSN 0300-9475. 77(6), p. 442–451. doi: 10.1111/sji.12049. Full text in Research Archive
• Troitskaya, Maria P.; Baysa, Anton; Vaage, Ingvar Jarle; Sand, Kristin Larsen; Maghazachi, Azzam & Valen, Guro (2012). IL-17 level is reduced during acute myocardial infarction. Role of chemokine receptor expression in monocytes and their in vitro chemotaxis towards chemokines. Toxins. 4(12), p. 1427–1439. doi: 10.3390/toxins4121427. Full text in Research Archive
• Rolin, Johannes; Sand, Kristin Larsen; Knudsen, Eirunn & Maghazachi, Azzam (2010). FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells and dendritic cells but not on cytokine release. Cancer Immunology and Immunotherapy. ISSN 0340-7004. 59(4), p. 575–586. doi: 10.1007/s00262-009-0775-7. Full text in Research Archive
• Sand, Kristin Larsen; Knudsen, Eirunn; Rolin, Johannes; Al-Falahi, Yassin & Maghazachi, Azzam (2009). Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 66(8), p. 1446–1456. doi: 10.1007/s00018-009-8726-1. Full text in Research Archive
• Al-Falahi, Yassin; Sand, Kristin Larsen; Knudsen, Eirunn; Damaj, Bassam; Rolin, Johannes & Maghazachi, Azzam (2009). Splenic natural killer cell activity in two models of experimental neurodegenerative diseases. Journal of Cellular and Molecular Medicine. ISSN 1582-1838. 13(8b), p. 2693–2703. doi: 10.1111/j.1582-4934.2008.00640.x. Full text in Research Archive
• Rolin, Johannes; Sand, Kristin Larsen; Knudsen, Eirunn & Maghazachi, Azzam (2009). FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells and dendritic cells but not on cytokine release. Cancer Immunology and Immunotherapy. ISSN 0340-7004. doi: 10.1007/s00262-009-0775-7. Full text in Research Archive
• Jakobsen, CH; Pettersen, Caroline Hild; Størvold, Gro Leite; Bremseth, Hilde; Follestad, Turid & Sand, Kristin [Show all 13 contributors for this article] (2008). DHA induces ER stress and growth arrest in human colon cancer cells: association with cholesterol and calcium homeostasis. Journal of Lipid Research. ISSN 0022-2275. 49, p. 2089–2100. doi: 10.1194/jlr.M700389-JLR200. Full text in Research Archive
• Schønberg, Svanhild Margrethe Arentz; Jakobsen, Caroline Hild; Bremseth, Hilde; Olsen, Karina Standahl; Lundemo, Anne Gøril & Follestad, Turid [Show all 9 contributors for this article] (2005). Endoplasmic reticulum stress induced by DHA leads to growth arrest of human colon cancer cells. Chemistry and Physics of Lipids. ISSN 0009-3084. 136(2), p. 101–101. Full text in Research Archive
• De, Blasio Birgitte Freiesleben; Røttingen, John-Arne; Sand, Kristin Larsen; Giaever, I & Iversen, Jens Gustav Heber (2004). Global, synchronous oscillations in cytosolic calcium and adherence in bradykinin-stimulated Madin-Darby canine kidney cells. Acta Physiologica Scandinavica. ISSN 0001-6772. 180, p. 335–346. Full text in Research Archive
• Melien, Øyvind; Nilssen, Laila Sortvik; Dajani, Olav Faial; Sand, Kristin Larsen; Sandnes, Dagny Lise & Iversen, Jens Gustav [Show all 7 contributors for this article] (2002). Ca2+-mediated activation of ERK in hepatocytes by norepinephrine and prostaglandin F2-alpha: role of calmodulin and src kinases. BMC Cell Biology. 3(5). Full text in Research Archive
• Aas, Vigdis; Algerøy, Siri; Sand, Kristin Larsen & Iversen, Jens Gustav (2001). Fibronectin Promotes Calcium Signaling by Interferon-gamma in Human Neutrophils via G-protein and Sphingosine Kinase-Dependent Mechanisms. Cell Adhesion and Communication. ISSN 1061-5385. 8(3), p. 125–138. Full text in Research Archive Show summary

  A common intracellular signal activating polymorphonuclear leukocyte (PMN) in inflammation is a change in cytosolic calcium concentration. Previously, we have shown that interferon-gamma (IFN-gamma) induces transient calcium signals in PMN, but only after intracellular calcium store depletion. Using a digital imaging system, we show that adhesion of PMN is critical for IFN-gamma induced calcium signals, and when attached to the optimal coating, the calcium signals are evoked even in presence of extracellular calcium, i.e. non-depleted calcium stores. Adhesion to fibronectin, pure or extracted from plasma by gelatin, improved the IFN-gamma responses compared with serum, plasma or vitronectin coats. In accordance with previous observations, IFN-gamma induced calcium signals in fibronectin adherent cells were totally abolished by the G-protein inhibitor pertussis toxin and were also clearly depressed by pertussis toxin and the sphingosine kinase inhibitors dimethylsphingosine (DMS) and N-acetyl-D-sphingosine (N-Ac-Sp). PMN contact with fibronectin alone, measured in cells sedimenting onto a fibronectin coated surface or by addition of fibronectin to glass adherent cells, evoked transient calcium signals in PMN. However, they were also clearly depressed by pertussis toxin and the sphingosine kinase inhibitors DMS, dihydrosphingosine (DHS), and N-Ac-Sp. When the product of sphingosine kinase activity, sphingosine 1-phosphate (S 1-P), was added to the cells, similar calcium signals were induced, which were dependent on a pertussis toxin sensitive G-protein activity. Finally, addition of S 1-P to the cells prior to stimulation with IFN-gamma partly mimicked the priming effect of fibronectin. In conclusion, fibronectin contact evokes by itself a calcium signal in PMN and further promotes calcium signalling by IFN-gamma. We suggest that fibronectin might activate sphingosine kinase and the sphingosine 1-phosphate, thereby generated, induce a calcium signal via a G-protein dependent mechanism. Apparently, sphingosine kinase activity is also involved in IFN-gamma induced calcium signals.

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• Benestad, Haakon Breien; Sand, Kristin Larsen & Bruusgaard, Jo C. (2018). Less than recommended training of aerobic fitness and muscle strength: What to expect? Acta Physiologica. ISSN 1748-1708. 224(4). doi: 10.1111/apha.13104. Full text in Research Archive
• Aas, Vigdis; Algerøy, Siri; Sand, Kristin Larsen & Iversen, Jens Gustav (2000). Fibronectin elicits a cytosolic calcium signal dependent on sphingosine kinase activity. Full text in Research Archive Show summary

  Fibronectin elicits a cytosolic calcium signal dependent on sphingosine kinase activity in neutrophils Vigdis Aas*, Siri Algerøy*, Kristin Larsen# and Jens-Gustav Iversen# *Department of pharmacology, School of pharmacy, University of Oslo, #Department of physiology, Institute of basic medical sciences, University of Oslo. Migration of neutrophils (PMN) towards inflammatory sites involves cell contact with extracellular matrix proteins like fibronectin (FN). The interaction with fibronectin has been reported to be a co-stimulatory signal that supports PMN activation. We have recently shown that the cytokine interferon-g (IFN-g) induces cytosolic calcium signals in human neutrophils adherent to fibronectin coated surfaces, but not in PMN adherent to uncoated glass surfaces. In an attempt to understand how adhesion to FN promote calcium signalling by IFN-g, we have investigated the effects of FN on PMN calcium metabolism. Registration of cytosolic calcium concentration in single fura-2 loaded cells was performed with a digital imaging technique. Baseline cytosolic calcium concentration in cells adherent to FN did not differ from cells adherent to glass or plasma. As assessed by store depletion with thapsigargin, there were no indications that adhesion to FN affected PMN calcium storage. However, when cells adherent to uncoated surfaces were stimulated with a FN- or a RGD-solution, transient calcium signals were evoked in 32 % and 62 % of the cells, respectively. In addition, PMN falling down onto FN-coated coverslips showed marked intracellular calcium signals when establishing contact with the FN-surface. Falling down onto FN-coating 85 % of the cells responded with an increase in cytosolic calcium concentration > 100 nM, average 309 ± 9 nM, compared to 57 % on plasma-coating and 32 % on uncoated coverslips. The FN-induced calcium signals were partly dependent on a pertussis-toxin sensitive G-protein, while they were totally abolished by the sphingosine kinase inhibitors N,N-dimethylsphingosine (DMS) and N-acetyl-D-sphingosine (N-Ac-Sp). Stimulation of PMN with the product of sphingosine kinase, sphingosine-1-phosphate, also induced transient cytosolic calcium signals which were dependent on a pertussis toxin sensitive G-protein. These data suggest that FN-attachment induces calcium signals in PMN, presumably by sphingosine kinase mediated generation of sphingosine-1-phosphate.

• Melien, Øyvind; Nilssen, Laila Sortvik; Dajani, Olav Faial; Sand, Kristin Larsen; Iversen, Jens Gustav & Sandnes, Dagny Lise [Show all 7 contributors for this article] (2000). A Role for Calmodulin and Src Kinases in Ca2+ - dependent activation of ERK in Hepatocytes by Norepinephrine and Prostaglandine F2Aalfa. Full text in Research Archive

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