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Andersson, Eva-Lotta
Publications (2 of 2) Show all publications
Lindquist, S., Andersson, E.-L., Lundberg, L. & Hernell, O. (2012). Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents. PLoS ONE, 7(10), e47006
Open this publication in new window or tab >>Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents
2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10, p. e47006-Article in journal (Refereed) Published
Abstract [en]

Objective: The present study aimed to explore the hypothesis that bile salt-stimulated lipase (BSSL), in addition to being a key enzyme in dietary fat digestion during early infancy, plays an important role in inflammation, notably arthritis. Methods: Collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rodents are commonly used experimental models that reproduce many of the pathogenic mechanisms of human rheumatoid arthritis, i.e. increased cellular infiltration, synovial hyperplasia, pannus formation, and erosion of cartilage and bone in the distal joints. We used the CIA model to compare the response in BSSL wild type (BSSL-WT) mice with BSSL-deficient 'knock-out' (BSSL-KO) and BSSL-heterozygous (BSSL-HET) littermates. We also investigated if intraperitoneal injection of BSSL-neutralizing antibodies affected the development or severity of CIA and PIA in mice and rats, respectively. Results: In two consecutive studies, we found that BSSL-KO male mice, in contrast to BSSL-WT littermates, were significantly protected from developing arthritis. We also found that BSSL-HET mice were less prone to develop disease compared to BSSL-WT mice, but not as resistant as BSSL-KO mice, suggesting a gene-dose effect. Moreover, we found that BSSL-neutralizing antibody injection reduced both the incidence and severity of CIA and PIA in rodents. Conclusion: Our data strongly support BSSL as a key player in the inflammatory process, at least in rodents. It also suggests the possibility that BSSL-neutralizing agents could serve as a therapeutic model to reduce the inflammatory response in humans.

Place, publisher, year, edition, pages
San Fransisco, USA: Public Library Science, 2012
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-61775 (URN)10.1371/journal.pone.0047006 (DOI)000309807700046 ()
Available from: 2012-11-27 Created: 2012-11-26 Last updated: 2018-06-08Bibliographically approved
Andersson, E.-L., Hernell, O., Bläckberg, L., Fält, H. & Lindquist, S. (2011). Bile salt-stimulated lipase and pancreatic lipase-related protein 2: key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line. Journal of Lipid Research, 52(11), 1949-1956
Open this publication in new window or tab >>Bile salt-stimulated lipase and pancreatic lipase-related protein 2: key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line
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2011 (English)In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 52, no 11, p. 1949-1956Article in journal (Refereed) Published
Abstract [en]

In rodents, bile salt-stimulated lipase (BSSL) and pancreatic lipase-related protein 2 (PLRP2) are the dominant lipases expressed in the exocrine pancreas in early life, when milk is the main food. The aim of the present study was to evaluate if BSSL and PLRP2 are also key enzymes in neonatal intestinal fat digestion. Using Caco-2 cells as a model for the small intestinal epithelium, purified human enzymes were incubated in the apical chamber with substrates and bile salt concentrations resembling the milieu of the small intestine of newborn infants. BSSL and PLRP2 hydrolyzed triglycerides (TG) to free fatty acids (FA) and glycerol. The cells took up the FA, which were reesterfied to TG. Together, BSSL and PLRP2 have a synergistic effect, increasing cellular uptake 4-fold compared to the sum of each lipase alone. A synergistic effect was also observed with retinyl ester as a substrate. PLRP2 hydrolyzed cholesteryl ester but not as efficiently as BSSL, and the two had an additive rather than synergistic effect. We conclude the key enzymes in intestinal fat digestion are different in newborns than later in life. Further studies are needed to fully understand this difference and its implication for designing optimal neonatal nutrition.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2011
Keywords
Bile acids and salts, Digestion, Fatty acid, Lipase, Nutrition, Triglycerides, Caco-2 cells, Fat, Newborn
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-46582 (URN)10.1194/jlr.M015685 (DOI)21865348 (PubMedID)
Available from: 2011-09-06 Created: 2011-09-06 Last updated: 2018-06-08Bibliographically approved
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