Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells

B. Salh, K. Assi, S. Huang, L. O'Brien, U. Steinbrecher, A. Gómez-Muñoz

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.

Original languageEnglish (US)
Pages (from-to)790-799
Number of pages10
JournalJournal of Leukocyte Biology
Volume72
Issue number4
Publication statusPublished - Oct 1 2002

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Keywords

  • Apoptosis
  • MAPK
  • Macrophages
  • Necrosis
  • PLD

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Salh, B., Assi, K., Huang, S., O'Brien, L., Steinbrecher, U., & Gómez-Muñoz, A. (2002). Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells. Journal of Leukocyte Biology, 72(4), 790-799.