Production of reactive oxygen intermediates following CD40 ligation correlates with c-Jun N-terminal kinase activation and IL-6 secretion in murine B lymphocytes

Jong Ran Lee, Gary A. Koretzky

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Recent studies indicate that reactive oxygen intermediates (ROI) serve as second messengers in cell signaling. ROI have been implicated in the activation of NF-κB as well as c-Jun N-terminal kinase (JNK) in response to IL-1 and TNF-α stimulation. In this report we examine whether intracellular ROI are involved in CD40 receptor signaling. We show that CD40 engagement on resting splenic B lymphocytes and murine B lymphoma WEHI 231 cells generates ROI. Blocking ROI production by preincubation with the antioxidant N-acetyl-L-cysteine inhibits JNK activation, NF-κB-driven luciferase activity, and IL-6 secretion following CD40 ligation, suggesting a role for ROI in CD40-mediated signaling events. Furthermore, transfection of WEHI 231 cells with a plasmid encoding Mn-superoxide dismutase interferes with CD40-induced NF-κB activation, providing further support for ROI involvement in this pathway. Collectively, these data demonstrate that ROI may serve as second messengers linking CD40 engagement on B cells to important downstream activation events.

Original languageEnglish
Pages (from-to)4188-4197
Number of pages10
JournalEuropean Journal of Immunology
Volume28
Issue number12
DOIs
StatePublished - Dec 1998

Keywords

  • c-Jun N-terminal kinase
  • CD40
  • IL-6
  • NF-κB
  • Reactive oxygen intermediate

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