The inhibitory action of sodium arsenite on lipopolysaccharide-induced nitric oxide production in RAW 267.4 Macrophage cells: A role of Raf-1 in lipopolysaccharide signaling

D. Chakravortty, Y. Kato, T. Sugiyama, N. Koide, M. M. Mu, T. Yoshida, T. Yokochi

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

The effect of sodium arsenite (SA) on LPS-induced NO production in RAW 267.4 murine macrophage cells was studied. SA pretreatment of LPS-stimulated RAW cells resulted in a striking reduction in NO production. No significant difference in LPS binding was observed between RAW cells pretreated with SA and control untreated RAW cells, suggesting that SA might impair the intracellular signal pathway for NO production. SA inhibited LPS-induced NF-κB activation by preventing loss of IκB-α and -β. Furthermore, SA blocked phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), but not phosphorylation of p38 and c-Jun N-terminal kinase. SA treatment resulted in the disappearance of Raf-1, suggesting that it might cause the inhibition of the Erk1/2 mitogen-activated protein (MAP) kinase pathway. The SA-mediated loss of Raf-1 also abolished LPS-induced NF-κB activation as well as the Erk1/2 pathway. The dominant negative mutant of MAP kinase kinase 1 inhibited both NO production and NF-κB activation in LPS-stimulated RAW cells. Taken together, these results indicate that the inhibitory action of SA on NO production in LPS-stimulated macrophages might be due to abrogation of inducible NO synthase induction, and it might be closely related to inactivation of the NF-κB and Erk1/2 MAP kinase pathways through loss of Raf-1.

Original languageEnglish
Pages (from-to)2011-2017
Number of pages7
JournalJournal of Immunology
Volume166
Issue number3
DOIs
Publication statusPublished - 01-02-2001

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The inhibitory action of sodium arsenite on lipopolysaccharide-induced nitric oxide production in RAW 267.4 Macrophage cells: A role of Raf-1 in lipopolysaccharide signaling'. Together they form a unique fingerprint.

Cite this