Production of reactive oxygen intermediates following CD40 ligation correlates with c-Jun N-terminal kinase activation and IL-6 secretion in murine B lymphocytes
✍ Scribed by Jong Ran Lee; Gary A. Koretzky
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 158 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Recent studies indicate that reactive oxygen intermediates (ROI) serve as second messengers in cell signaling. ROI have been implicated in the activation of NF-O B as well as c-Jun N-terminal kinase (JNK) in response to IL-1 and TNF- § 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-Lcysteine inhibits JNK activation, NF-O B-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-O B 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.