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Role of caspase in CD80 expression of superantigen-stimulated monocytes
Fumiaki Shinohara1, Keiko Sato, Maiko Suzuki
1Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai 980-8575, Japan.
Abstract:
In this study, we demonstrated evidence for the induction of CD80+ monocytes by staphylococcal enterotoxin B (SEB) via caspase actions. Pre-treatment with pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappaB, resulted in a significant reduction in the percentage of SEB- and interferon-gamma (IFN-gamma) (produced by SEB) -induced CD80+ monocytes. SEB and IFN-gamma activated NF-kappaB, which was inhibited by PDTC. SEB induced the activation of caspase-3 and -8, and pre-treatment with z-VAD-fmk, a broad-spectrum inhibitor of caspases, prevented the induction of apoptosis. Treating with z-VAD-fmk resulted in a reduction of the generation of CD80+ monocytes. These results indicated that CD80 driven by NF-kappaB is regulated by the enzymatic actions of caspases, which allows monocytes to participate in massive T-cell activation.
Insights
Staphylococcal enterotoxin B (SEB) induces CD80+ monocytes via caspase activation. Inhibiting caspases or NF-kappaB reduces this monocyte response, crucial for T-cell activation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Staphylococcal enterotoxin B (SEB) is a superantigen known to induce massive T-cell activation.
- Monocytes play a critical role in immune responses, including antigen presentation.
Purpose of the Study:
- To investigate the mechanism by which SEB induces CD80+ monocytes.
- To elucidate the role of caspases and NF-kappaB in SEB-mediated monocyte activation.
Main Methods:
- ব্যবহৃত হয়েছে স্ট্যাফিলোকক্কাল এন্টারোটক্সিন বি (SEB) এবং ইঁদুর মনোসাইট।
- NF-kappaB ইনহিবিটর (PDTC) এবং ক্যাস্পেস ইনহিবিটর (z-VAD-fmk) ব্যবহার করে পরীক্ষা করা হয়েছে।
- ফ্লো সাইটোমেট্রি ব্যবহার করে CD80+ মনোসাইটের শতাংশ পরিমাপ করা হয়েছে।
Main Results:
- SEB-induced CD80+ monocytes were significantly reduced by PDTC, an NF-kappaB inhibitor.
- SEB activated both NF-kappaB and caspases (-3 and -8).
- Caspase inhibition by z-VAD-fmk prevented apoptosis and reduced CD80+ monocyte generation.
Conclusions:
- CD80 expression on monocytes induced by SEB is regulated by caspase activity.
- NF-kappaB activation, downstream of caspase action, is essential for SEB-induced CD80+ monocyte generation.
- This pathway highlights a novel mechanism for monocyte involvement in SEB-driven T-cell activation.
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