Abstract
Ricin toxin binding subunit B (RTB) is one of the subunits of the ricin protein. RTB has been used as adjuvant, but little is known about its mechanism. In this study, we found that RTB increased not only nitric oxide (NO) release, but also tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in mouse macrophage cell line RAW264.7 cells. They subsequently exhibited enhanced ConA-induced T-cell and LPS-induced B-cell proliferative responses. We also examined the cytokines that were produced from splenocytes following in vitro RTB administration. Increased levels of IL-2, interferon (IFN)-γ and TNF-α were observed, while IL-4 and IL-5 were unaffected. These results demonstrate that recombinant RTB can act on the immune system and activate T-cells by introducing a Th1 immune response. Th1 cells might be the primary cellular target affected by RTB. Our results suggest that the recombinant RTB can promote the activation of macrophages and has a beneficial effect on immunomodulatory activity.
Highlights
IntroductionRicin toxin belongs to the type II ribosome-inactivating protein family (type II RIPs)
Ricin is a heterodimeric protein toxin produced by the seeds of Ricinus communis
We investigate the functional activation of Ricin toxin binding subunit B (RTB) by analyzing the production of nitric oxide (NO), tumor necrosis factor (TNF)-α and IL-6 from mouse macrophage cell line RAW264.7 cells
Summary
Ricin toxin belongs to the type II ribosome-inactivating protein family (type II RIPs) It is composed of A and B chains that are joined by a disulfide bond [1]. RTB has been used as a target for antibody-based intervention therapeutics against infectious disease, and the enhancement of vaccines has been demonstrated [7,8,9]. Aside from these studies, the mechanism and immunogenicity of RTB remains poorly understood. Cell-mediated immune responses involve the activation of macrophages and the release of cytokines in response to the antigen. We analyzed mitogen response induced by RTB in splenocytes and splenocyte cytokine expression
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