Cytosolic phospholipase A2α has a crucial role in the pathogenesis of DSS-induced colitis in mice

Marina Rosengarten, Nurit Hadad, Yulia Solomonov, Sergio Lamprecht, Rachel Levy

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Colitis, an inflammation of the colon, is a well-characterized massive tissue injury. Cytosolic phospholipase A2α (cPLA2α) upregulation plays an important role in the development of several inflammatory diseases. The aim of the present study was to define the role of cPLA2α upregulation in the development of colitis. We used a mouse model of dextran sulfate sodium induced colitis. Immunoblotting analysis showed that cPLA2α and NF-κB were upregulated and activated in the colon from day 2 of colitis induction. This molecular event preceded the development of the disease, as determined by Disease Activity Index score, body weight, colon length, and the expression of colonic inflammatory markers, including neutrophil infiltration detected by myeloperoxidase and by NIMP-R14, ICAM-1, COX-2, iNOS upregulation and LTB4 and TNF-α secretion. Prevention of cPLA2α upregulation and activity in the colon by i.v. administration of specific antisense oligonucleotides against cPLA2α 1 day prior and every day of exposure to dextran sulfate sodium significantly impeded the development of the disease and prevented NF-κB activation, neutrophils infiltration into the colonic mucosa, and expression of proinflammatory proteins in the colon. Our results demonstrate a critical role of cPLA2α upregulation in inflammation and development of murine colitis.

Original languageEnglish
Pages (from-to)400-408
Number of pages9
JournalEuropean Journal of Immunology
Volume46
Issue number2
DOIs
StatePublished - 1 Feb 2016

Keywords

  • COX-2
  • Cytosolic phospholipase Aα (cPLAα)
  • DAI: Disease Activity Index
  • DSS-induced colitis
  • Inflammatory bowel disease (IBD)
  • Neutrophil NF-κB
  • TNF-α

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