• A role for the adaptor proteins TRAM and TRIF in toll-like receptor 2 signaling 

      Nilsen, Nadra; Gregory I., Vladimer; Stenvik, Jørgen; Ørning, Mathias Pontus; Zeid-Kilani, Maria Vanessa; Bugge, Marit; Bergstrøm, Bjarte; Conlon, Joseph; Husebye, Harald; Amy, Hise; Fitzgerald, Katherine A.; Espevik, Terje; Lien, Egil (Journal article; Peer reviewed, 2015)
      Toll-like receptors (TLRs) are involved in sensing invading microbes by host innate immunity. TLR2 recognizes bacterial lipoproteins/lipopeptides, and lipopolysaccharide activates TLR4. TLR2 and TLR4 signal via the ...
    • Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model 

      Rokstad, Anne Mari; Brekke, Ole Lars; Steinkjer, Bjørg; Ryan, Liv; Kolláriková, Gabriela; Strand, Berit Løkensgard; Skjåk-Bræk, Gudmund; Lacík, Igor; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2011)
      Alginate microbeads and microcapsules are presently under evaluation for future cell-based therapy. Defining their inflammatory properties with regard to humans is therefore essential. A lepirudine-based human whole blood ...
    • Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation 

      Ørning, Mathias Pontus; Hoem, Kine Samseth; Coron, Abba Elizabeth; Skjåk-Bræk, Gudmund; Mollnes, Tom Eirik; Brekke, Ole Lars; Espevik, Terje; Rokstad, Anne Mari (Journal article; Peer reviewed, 2016)
      The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere ...
    • Alpha-cyclodextrin inhibits cholesterol crystal-induced complement-mediated inflammation: A potential new compound for treatment of atherosclerosis. 

      Pilely, Katrine; Bakke, Siril Skaret; Palarasah, Yaseelan; Skjoedt, Mikkel-Ole; Bartels, Emil D.; Espevik, Terje; Garred, Peter (Peer reviewed; Journal article, 2019)
      Background and aims Cholesterol crystal (CC)-induced inflammation is a critical step in the development of atherosclerosis. CCs activate the complement system and induce an inflammatory response resulting in phagocytosis ...
    • Biocompatibility and Biotolerability Assessment of Microspheres Using a Whole Blood Model 

      Rokstad, Anne Mari; Strand, Berit Løkensgard; Espevik, Terje; Mollnes, Tom Eirik (Journal article, 2013)
      The whole blood model is a powerful method to determine the immediate inflammatory reactions towards foreign objects in general. This review focuses on the use of a lepirudin based whole blood model for evaluating microspheres ...
    • CD14 and complement crosstalk and largely mediate the transcriptional response to Escherichia coli in human whole blood as revealed by DNA microarray 

      Lau, Corinna; Nygård, Ståle; Fure, Hilde; Olstad, Ole Kristoffer; Holden, Marit; Lappegård, Knut Tore; Brekke, Ole Lars; Espevik, Terje; Hovig, Johannes Eivind; Mollnes, Tom Eirik (Journal article, 2015)
      Systemic inflammation like in sepsis is still lacking specific diagnostic markers and effective therapeutics. The first line of defense against intruding pathogens and endogenous damage signals is pattern recognition by ...
    • Chimeric Anti-CD14 IGG2/4 Hybrid Antibodies for Therapeutic Intervention in Pig and Human Models of Inflammation 

      Lau, Corinna; Gunnarsen, Kristin Støen; Høydahl, Lene Støkken; Andersen, Jan Terje; Berntzen, Gøril; Pharo, Anne Margrethe; Lindstad, Julie Katrine; Ludviksen, Judith K; Brekke, Ole Lars; Barratt-Due, Andreas; Nielsen, Erik Waage; Stokes, Christopher R.; Espevik, Terje; Sandlie, Inger; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2013)
      CD14 is a key recognition molecule of innate immune responses, interacting with several TLRs. TLR signaling cross-talks extensively with the complement system, and combined CD14 and complement inhibition has been proved ...
    • Cholesterol crystal-induced endothelial cell activation is complement-dependent and mediated by TNF 

      Nymo, Stig Haugset; Niyonzima, Nathalie; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2014)
      Cholesterol crystals are known to be a hallmark of atherosclerosis with recent studies demonstrating deposition of these crystals in early fatty streak formation as well as penetrating the intima following plaque rupture. ...
    • Cholesterol crystals activate the lectin complement pathway via ficolin-2 and mannose-binding lectin: Implications for the progression of atherosclerosis 

      Pilely, Katrine; Rosbjerg, Anne; Genster, Ninette; Gál, Peter; Pál, Gábor; Halvorsen, Bente; Holm, Sverre; Aukrust, Pål; Bakke, Siril Skaret; Sporsheim, Bjørnar; Nervik, Ingunn; Niyonzima, Nathalie; Bartels, Emil D.; Stahl, Gregory L.; Mollnes, Tom Eirik; Espevik, Terje; Garred, Peter (Journal article, 2016)
      Cholesterol crystals (CC) play an essential role in the formation of atherosclerotic plaques. CC activate the classical and the alternative complement pathways, but the role of the lectin pathway is unknown. We hypothesized ...
    • Cholesterol Crystals Induce coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor 

      Gravastrand, Caroline S.; Steinkjer, Bjørg; Halvorsen, Bente; Landsem, Anne; Skjelland, Mona; Jacobsen, Eva Astrid; Woodruff, Trent M.; Lambris, John D.; Mollnes, Tom Eirik; Brekke, Ole-Lars; Espevik, Terje; Rokstad, Anne Mari (Journal article; Peer reviewed, 2019)
      Cholesterol crystals (CC) are strong activators of complement and could potentially be involved in thromboinflammation through complement-coagulation cross-talk. To explore the coagulation-inducing potential of CC, we ...
    • Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis 

      Niyonzima, Nathalie; Bakke, Siril S.; Gregersen, Ida; Holm, Sverre; Sandanger, Øystein; Orrem, Hilde Lang; Sporsheim, Bjørnar; Ryan, Liv; Kong, Xiang Yi; Dahl, Tuva Børresdatter; Skjelland, Mona; Sørensen, Kirsten; Rokstad, Anne Mari A.; Yndestad, Arne; Latz, Eicke; Gullestad, Lars; Andersen, Geir Øystein; Damås, Jan Kristian; Aukrust, Pål; Mollnes, Tom Eirik; Halvorsen, Bente; Espevik, Terje (Peer reviewed; Journal article, 2020)
      Background: During atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) ...
    • Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response 

      Bösl, Korbinian; Giambelluca, Miriam; Haug, Markus; Bugge, Marit; Espevik, Terje; Kandasamy, Richard Kumaran; Bergstrøm, Bjarte Aune (Journal article; Peer reviewed, 2018)
      Innate immune signaling is essential to mount a fast and specific immune response to pathogens. Monocytes and macrophages are essential cells in the early response in their capacity as ubiquitous phagocytic cells. They ...
    • Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome 

      Thomas, Anub Mathew; Schjalm, Camilla; Nilsson, Per; Lindenskov, Paal Helge H.; Rørtveit, Runa; Solberg, Rønnaug; Saugstad, Ola Didrik; Berglund, Magnus M.; Strömberg, Patrik; Lau, Corinna; Espevik, Terje; Jansen, Johan Høgset; Castellheim, Albert; Mollnes, Tom Eirik; Barratt-Due, Andreas (Journal article; Peer reviewed, 2018)
      Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a ...
    • Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis 

      Hellerud, Bernt C; Orrem, Hilde L.; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas; Castellheim, Albert; Fure, Hilde; Bergseth, Grete; Christiansen, Dorte; Nunn, Miles A.; Espevik, Terje; Lau, Corinna; Brandtzæg, Petter; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2017)
      Background Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key ...
    • Combined inhibition of complement and CD14 attenuates bacteria-induced inflammation in human whole blood more efficiently than antagonizing the toll-like receptor 4-MD2 complex 

      Gustavsen, Alice; Nymo, Stig Haugset; Landsem, Anne; Christiansen, Dorte; Ryan, Liv; Husebye, Harald; Lau, Corinna; Pischke, Søren Erik; Lambris, John D.; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2016)
      Background. Single inhibition of the Toll-like receptor 4 (TLR4)–MD2 complex failed in treatment of sepsis. CD14 is a coreceptor for several TLRs, including TLR4 and TLR2. The aim of this study was to investigate the effect ...
    • Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis 

      Skjeflo, Espen Waage; Sagatun, Caroline; Dybwik, Knut; Aam, Sturla; Urving, Sven Haakon; Nunn, Miles A.; Fure, Hilde; Lau, Corinna; Brekke, Ole Lars; Huber-Lang, Markus; Espevik, Terje; Barratt-Due, Andreas; Nielsen, Erik Waage; Mollnes, Tom Eirik (Peer reviewed; Journal article, 2015)
      Introduction Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate ...
    • Complement activation by cholesterol crystals triggers a subsequent cytokine response 

      Niyonzima, Nathalie; Halvorsen, Bente; Sporsheim, Bjørnar; Garred, Peter; Aukrust, Pål; Mollnes, Tom Eirik; Espevik, Terje (Journal article; Peer reviewed, 2017)
      In the host a diverse collection of endogenous danger signals is constantly generated consisting of waste material as protein aggregates or crystalline materials that are recognized and handled by soluble pattern recognition ...
    • Complement component 5 does not interfere with physiological hemostasis but is essential for Escherichia coli-induced coagulation accompanied by Toll-like receptor 4. 

      Landsem, Anne; Fure, Hilde; Ludviksen, Judith K; Christiansen, Dorte; Lau, Corinna; Mathisen, Monica Dammen; Bergseth, Grete; Nymo, Stig Haugset; Lappegård, Knut Tore; Woodruff, T. M.; Espevik, Terje; Mollnes, Tom Eirik; Brekke, Ole-Lars (Journal article; Peer reviewed, 2018)
      There is a close cross‐talk between complement, Toll‐like receptors (TLRs) and coagulation. The role of the central complement component 5 (C5) in physiological and pathophysiological hemostasis has not, however, been fully ...
    • Complement component C5 and TLR molecule CD14 mediate heme-induced thromboinflammation in human blood 

      Thomas, Anub Mathew; Gerogianni, Alexandra; McAdam, Martin Berner; Fløisand, Yngvar; Lau, Corinna; Espevik, Terje; Nilsson, Per; Mollnes, Tom Eirik; Barratt-Due, Andreas (Journal article; Peer reviewed, 2019)
      Heme is a critical danger molecule liberated from hemeproteins in various conditions, including from hemoglobin in hemolytic diseases. Heme may cause thromboinflammatory damage by activating inflammatory and hemostatic ...
    • Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming 

      Zimmer, Sebastian; Grebe, Alena; Bakke, Siril Skaret; Bode, Niklas; Halvorsen, Bente; Ulas, Thomas; Skjelland, Mona; De Nardo, Dominic; Labzin, Larisa I.; Kerksiek, Anja; Hempel, Chris; Heneka, Michael T.; Hawxhurst, Victoria; Fitzgerald, Michael L.; Trebicka, Jonel; Björkhem, Ingemar; Gustafsson, Jan Åke; Westerterp, Marit; Tall, Alan R.; Wright, Samuel D.; Espevik, Terje; Schultze, Joachim L.; Nickenig, Georg; Lütjohann, Dieter; Latz, Eicke (Journal article, 2016)
      Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause ...