LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice

We have previously demonstrated that continuous infusion of low molecular weight (LMW) heparin delays autoantibody production and development of lupus nephritis in (NZBxNZW)F1 (B/W) mice. In this study we investigated the effect of LMW heparin on renal cytokine and chemokine expression and on nucleo...

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Main Authors: Annica Hedberg, Premasany Kanapathippillai, Ole Petter Rekvig, Kristin Andreassen Fenton
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2013/791262
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author Annica Hedberg
Premasany Kanapathippillai
Ole Petter Rekvig
Kristin Andreassen Fenton
author_facet Annica Hedberg
Premasany Kanapathippillai
Ole Petter Rekvig
Kristin Andreassen Fenton
author_sort Annica Hedberg
collection DOAJ
description We have previously demonstrated that continuous infusion of low molecular weight (LMW) heparin delays autoantibody production and development of lupus nephritis in (NZBxNZW)F1 (B/W) mice. In this study we investigated the effect of LMW heparin on renal cytokine and chemokine expression and on nucleosome-mediated activation of nucleosome-specific splenocytes. Total mRNA extracted from kidneys of heparin-treated or -untreated B/W mice was analysed by qPCR for the expression of several cytokines, chemokines, and Toll-like receptors. Splenocytes taken from B/W mice were stimulated with nucleosomes with or without the presence of heparin. Splenocyte cell proliferation as thymidine incorporation and the expression of costimulatory molecules and cell activation markers were measured. Heparin treatment of B/W mice reduced the in vivo expression of CCR2, IL1β, and TLR7 compared to untreated B/W mice. Nucleosome-induced cell proliferation of splenocytes was not influenced by heparin. The expression of CD80, CD86, CD69, CD25, CTLA-4, and TLR 2, 7, 8, and 9 was upregulated upon stimulation by nucleosomes, irrespective of whether heparin was added to the cell culture or not. In conclusion, treatment with heparin lowers the kidney expression of proinflammatory mediators in B/W mice but does not affect nucleosomal activation of splenocytes.
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spelling doaj-art-8c52773d39cd4ffe9176fb17946265932025-02-03T01:26:11ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/791262791262LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 MiceAnnica Hedberg0Premasany Kanapathippillai1Ole Petter Rekvig2Kristin Andreassen Fenton3RNA and Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, NorwayRNA and Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, NorwayRNA and Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, NorwayRNA and Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, NorwayWe have previously demonstrated that continuous infusion of low molecular weight (LMW) heparin delays autoantibody production and development of lupus nephritis in (NZBxNZW)F1 (B/W) mice. In this study we investigated the effect of LMW heparin on renal cytokine and chemokine expression and on nucleosome-mediated activation of nucleosome-specific splenocytes. Total mRNA extracted from kidneys of heparin-treated or -untreated B/W mice was analysed by qPCR for the expression of several cytokines, chemokines, and Toll-like receptors. Splenocytes taken from B/W mice were stimulated with nucleosomes with or without the presence of heparin. Splenocyte cell proliferation as thymidine incorporation and the expression of costimulatory molecules and cell activation markers were measured. Heparin treatment of B/W mice reduced the in vivo expression of CCR2, IL1β, and TLR7 compared to untreated B/W mice. Nucleosome-induced cell proliferation of splenocytes was not influenced by heparin. The expression of CD80, CD86, CD69, CD25, CTLA-4, and TLR 2, 7, 8, and 9 was upregulated upon stimulation by nucleosomes, irrespective of whether heparin was added to the cell culture or not. In conclusion, treatment with heparin lowers the kidney expression of proinflammatory mediators in B/W mice but does not affect nucleosomal activation of splenocytes.http://dx.doi.org/10.1155/2013/791262
spellingShingle Annica Hedberg
Premasany Kanapathippillai
Ole Petter Rekvig
Kristin Andreassen Fenton
LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice
Clinical and Developmental Immunology
title LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice
title_full LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice
title_fullStr LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice
title_full_unstemmed LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice
title_short LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice
title_sort lmw heparin prevents increased kidney expression of proinflammatory mediators in nzbxnzw f1 mice
url http://dx.doi.org/10.1155/2013/791262
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AT olepetterrekvig lmwheparinpreventsincreasedkidneyexpressionofproinflammatorymediatorsinnzbxnzwf1mice
AT kristinandreassenfenton lmwheparinpreventsincreasedkidneyexpressionofproinflammatorymediatorsinnzbxnzwf1mice