Modulation of nitric oxide, hydrogen peroxide and cytokine production in a clonal macrophage model by the trichothecene vomitoxin (deoxynivalenol).
Characterization of how vomitoxin (VT) and other trichothecenes affect macrophage regulatory and effector function may contribute to improved understanding of mechanisms by which these mycotoxins impact the immune system. The RAW 264.7 murine cell line was used as a macrophage model to assess effects of the VT on proliferation and the production of nitric oxide (NO), hydrogen peroxide (H2O2) and cytokines. Using the MTT cleavage assay, VT at concentrations of 50 ng/ml or higher was found to significantly decrease proliferation and viability of RAW 264.7 cells without stimulation or with stimulation by lipopolysaccharide (LPS) or interferon (IFN)-gamma. In the absence of an activation agent, VT (25-250 ng/ml) had negligible effects on the production of NO, H2O2, and cytokines. Upon activation with LPS at concentrations of 10 to 100 ng/ml, VT at 25-100 ng/ml markedly enhanced production of H2O2 but was inhibitory at 250 ng/ml. VT enhancement of H2O2 production was observed as early as 12 h after LPS stimulation. When IFN-gamma was used as the stimulant, VT (25-250 ng/ml) delayed peak H2O2 production. VT (25-250 ng/ml) also markedly decreased NO production in cells activated with LPS or IFN-gamma. Interestingly, VT superinduced TNF-alpha and IL-6 production in LPS-stimulated cells and also elevated TNF-alpha in IFN-gamma stimulated cells. These results suggest that VT can selectively and concurrently upregulate or downregulate critical functions associated with activated macrophages.
Ji
G E
GE
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224, USA.
Park
S Y
SY
Wong
S S
SS
Pestka
J J
JJ
D000704:Analysis of Variance; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D014255:Trichothecenes / Q000494:pharmacology*
D016207:Cytokines; D014255:Trichothecenes; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C007262:deoxynivalenol