Gold sodium thiomalate (GSTM) inhibits lipopolysaccharide stimulated tumor necrosis factor-α through ceramide pathway

Ashutosh Kumar Mangalam, Amita Aggarwal, Sita Naik

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

TNF-α has emerged as the major pro-inflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). LPS is a potent stimulator of TNF-α production by human monocytes. Ceramide, a structural homolog of LPS and a second messenger in the sphingomyelin signal transduction pathway has been shown to stimulate TNF-α production from murine macrophages. We have previously shown that GSTM, an anti-rheumatic drug inhibits LPS stimulated TNF-α production by normal PBMCs. We studied the ability of ceramide to stimulate TNF-α production by human PBMCs and the mechanism of action of GSTM on ceramide and LPS induced TNF-α production. LPS induced significant TNF-α production in PBMCs and THP-1. However, C2 ceramide stimulated TNF-α production in 5 of 10 PBMCs (ceramide responder); it did not do so in the other 5 PBMCs (ceramide non-responder) or the THP-1 cell line. GSTM inhibited LPS stimulated TNF-α productions in PBMCs of all 5 ceramide responders both at protein and mRNA expression level. We also found that GSTM inhibited LPS induced NF-κB level only in ceramide responder. Thus, we for the first time report that GSTM inhibits LPS stimulated TNF-α production through ceramide pathway and anti-inflammatory activity of GSTM in treatment of RA may depend on its ability to inhibit NF-κB activation and TNF-α production.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalCellular Immunology
Volume219
Issue number1
DOIs
StatePublished - Dec 1 2002

Keywords

  • Ceramide
  • Cytokines
  • Human
  • Inflammation
  • Lipopolysaccharide
  • RT-PCR and transcription factors

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Gold sodium thiomalate (GSTM) inhibits lipopolysaccharide stimulated tumor necrosis factor-α through ceramide pathway'. Together they form a unique fingerprint.

  • Cite this