alexa Lipopolysaccharide and ceramide use divergent signaling pathways to induce cell death in murine macrophages.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular Biomarkers & Diagnosis

Author(s): Lakics V, Vogel SN

Abstract Share this page

Abstract Ceramide is a well-known apoptotic agent that has been implicated in LPS signaling. Therefore, we examined whether LPS-induced macrophage cytotoxicity is mediated by mimicking ceramide. Both LPS and the cell-permeable ceramide analogue, C2 ceramide, induced significant cell death in IFN-gamma-activated, thioglycollate-elicited peritoneal macrophages after 48 and 24 h, respectively. Ceramide-induced cell death was neither accompanied by DNA fragmentation nor phosphatidyl serine externalization, characteristics of apoptosis. In contrast, LPS induced a significant fraction of cells to undergo apoptosis, as demonstrated by DNA fragmentation and quantified by DNA analysis on FACS, yet the majority of the cells died in a necrotic fashion. C3H/HeJ Lps(d) macrophages were resistant to LPS-induced cell death and less sensitive to C2 ceramide-evoked cytotoxicity, when compared with Lps(n) macrophages. C2 ceramide plus IFN-gamma failed to activate release of nitric oxide (NO.), whereas LPS-induced cell death, but not C2-induced cytotoxicity, was blocked by an inhibitor of inducible NO. synthase (iNOS), NG-monomethyl-L-arginine. Macrophages from IFN regulatory factor-1 (-/-) mice shown previously to respond marginally to LPS plus IFN-gamma to express iNOS mRNA and NO., were refractory to LPS plus IFN-gamma-induced cytotoxicity and apoptosis. These data suggest that although LPS may mimic certain ceramide effects, signal transduction events that lead to cytotoxicity, as well as the downstream mediators, diverge.
This article was published in J Immunol and referenced in Journal of Molecular Biomarkers & Diagnosis

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 9th International Conference and Expo on Molecular & Cancer Biomarkers
    August 23-24, 2017 Birmingham, UK
  • 2nd International Conference on Medical Imaging and Diagnosis
    London, UK
  • 22nd International Conference on Cancer Drugs and Therapeutics
    Paris, France
  • International Conference on Oncology Nursing and Cancer Care
    Singapore City, Singapore
  • World Summit on Cell Signalling and Cancer Therapy
    Toronto, Canada
  • International Conference on Radiology and Imaging
    New York, USA

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version