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Author McKallip, Robert J. ♦ Lombard, Catherine ♦ Jingping, Sun ♦ Ramakrishnan, Rupal
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ APOPTOSIS ♦ IMMUNOSUPPRESSION ♦ LYMPHOCYTES ♦ OXYGEN ♦ ANIMAL CELLS ♦ BIOLOGICAL MATERIALS ♦ BLOOD ♦ BLOOD CELLS ♦ BODY FLUIDS ♦ CONNECTIVE TISSUE CELLS ♦ ELEMENTS ♦ LEUKOCYTES ♦ MATERIALS ♦ NONMETALS ♦ SOMATIC CELLS
Abstract Extracts from plants containing plumbagin (PLB) continue to be used as a treatment of a number of chronic immunologically-based diseases. However, most of these claims are supported only by anecdotal evidence with few scientific reports describing the mechanism of action or the efficacy of plumbagin in the suppression of the immune response. In the current study, we tested the hypothesis that plumbagin-induced suppression of the immune response was mediated through the induction of apoptosis. Splenocytes from C57BL/6 mice cultured in the presence of 0.5 {mu}M or greater concentrations of PLB significantly reduced proliferative responses to mitogens, including anti-CD3 mAbs, concanavalin A (Con A), lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) in vitro. Exposure of naive and activated splenocytes to PLB led to a significant increase in the levels of apoptosis. In addition, PLB treatment led to a significant increase in the levels of reactive oxygen species (ROS) in naive and activated splenocytes. Furthermore, treatment with the ROS scavenger, N-acetylcysteine (NAC), prevented PLB-induced apoptosis, suggesting a role of ROS in PLB-induced apoptosis. PLB-induced apoptosis led to ROS-mediated activation of both the extrinsic and intrinsic apoptotic pathways. In addition, plumbagin led to increased expression of Fas. Finally, treatment of mice with PLB (5 mg/kg) led to thymic and splenic atrophy as well as a significant suppression of the response to SEB and dinitroflourobenzene (DNFB) in vivo. Together, these results suggest that plumbagin has significant immunosuppressive properties which are mediated by generation of ROS, upregulation of Fas, and the induction of apoptosis.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2010-08-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 247
Issue Number 1


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