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Roles of TNF‐alpha and IL‐1 in mediating the inflammatory responses to ricin in macrophages
Author(s) -
Korcheva Veselina Borisova,
Wong John,
Magun Bruce
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a649-d
Subject(s) - tumor necrosis factor alpha , ricin , alpha (finance) , immunology , inflammation , chemistry , medicine , biochemistry , toxin , clinical psychology , construct validity , psychometrics
Because of its lethal effects, ease of preparation, and ability to be delivered by aerosolization, ricin has been developed as a lethal weapon by various terrorist groups. When introduced into the pulmonary system of rodents, ricin causes pathological changes in the lung that are known to occur in acute respiratory distress syndrome (ARDS). Early response cytokines such as TNF‐α and IL‐1 are known to play a critical role in the pathogenesis of ARDS. Ricin directly induced the release of these proinflammatory cytokines and the transcriptional activation of the genes that encode them in vitro and in vivo . Macrophages, considered to be an upstream regulator of inflammatory cascades, may play a central role in the pathogenesis and the development of ricin‐induced ARDS because of their ability to make and secrete proinflammatory cytokines. Exposure of macrophages to ricin in vitro leads to activation of stress‐activated protein kinases, increased expression of TNF‐α and IL‐1 mRNAs, and subsequent increase in the secretion of TNF‐α and IL‐1 proteins. We asked whether primary macrophages derived from wild‐type mice and mice deficient in TNF‐α and IL‐1 signaling respond differently in vitro to the proinflammatory effects of ricin. We treated bone marrow‐derived macrophages with graded concentrations of ricin. RNA was extracted and subjected to real‐time RT‐PCR analysis. Macrophages isolated from mutant mice displayed altered expression of mRNAs encoding selected inflammatory genes. These data suggest the importance of TNF‐α and IL‐1 in modulating ricin‐mediated inflammatory responses in macrophages.