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Sökning: onr:"swepub:oai:DiVA.org:oru-54101" > Functional Analyses...

  • Assadi, GhazalehKarolinska Institutet (författare)

Functional Analyses of the Crohn's Disease Risk Gene LACC1

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • 2016-12-13
  • San Francisco, USA :Public Library of Science,2016
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-54101
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-54101URI
  • https://doi.org/10.1371/journal.pone.0168276DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-140421URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135105705URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agency:Karolinska Institutet KID PhD fellowship
  • Background: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression.Methods: We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function.Results: FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems.Conclusion: FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Vesterlund, LiselotteKarolinska Institutet (författare)
  • Bonfiglio, FerdinandoKarolinska Institutet (författare)
  • Mazzurana, LucaKarolinska Institutet (författare)
  • Cordeddu, LinaDepartment of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden (författare)
  • Schepis, DanikaRheumatology unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (författare)
  • Mjösberg, JennyKarolinska Institutet (författare)
  • Ruhrmann, SabrinaDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (författare)
  • Fabbri, AlessiaKarolinska Institutet (författare)
  • Vukojevic, VladanaKarolinska Institutet (författare)
  • Percipalle, PiergiorgioStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,New York University Abu Dhabi, United Arab Emirates(Swepub:su)pperc (författare)
  • Salomons, Florian A.Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (författare)
  • Laurencikiene, JurgaKarolinska Institutet (författare)
  • Törkvist, LeifKarolinska Institutet (författare)
  • Halfvarson, Jonas,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden(Swepub:oru)jshn (författare)
  • D'Amato, MauroKarolinska Institutet (författare)
  • Karolinska InstitutetDepartment of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:PLOS ONESan Francisco, USA : Public Library of Science11:121932-6203

Internetlänk

Hitta via bibliotek

  • PLOS ONE (Sök värdpublikationen i LIBRIS)

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