Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production.

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Erdogan S, Tosyali E, Duzguner V, Kucukgul A, Aslantas O, Celik S

Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production.

Res Vet Sci. 2010 Apr;88(2):218-26. doi: 10.1016/j.rvsc.2009.09.002. Epub 2009 Oct 8.

PubMed ID

19818462 [ View in PubMed

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Abstract

Brucella species are able to survive and replicate within the phagocytic cells and cause chronic infections in domestic animals and humans. Modulation of programmed cell death by Brucella spp. may be one of the reasons of the chronicity of the infection. In this study, whether cisplatin treatment, an apoptotic anticancer agent, would enhance the host resistance against Brucella melitensis-infected human macrophage-like cells was investigated. The infection neither induced inflammation nor oxidative stress. But, Brucella caused a decrease in infected macrophage viability of 36% at 48 h postinfection (p.i.) as compared with uninfected cells. Treatment of infected macrophages with 20 microM cisplatin for 48 h caused a large increase in nitric oxide (NO) levels in a time-dependent manner via induction of iNOS transcription. Cisplatin also enhanced glutathione peroxidase, myeloperoxidase and xanthine oxidase activities, providing evidence of generation of reactive free radicals. N-acetylcysteine was able to decrease cisplatin-induced NO, and prevented the agent-induced apoptosis, similar to effects found in l-NAME (N(G)-nitro-l-arginine methyl ester) treatment. Cisplatin stimulated inflammation through the induction of TNF-alpha and IL-12 secretion, and down-regulated Brucella-stimulated IL-10 transcription. The number of infected cells and their viability were decreased by 80% at 48 h p.i. by cisplatin in comparison with infected cells. Similar to this result, cisplatin treatment resulted in reduced intracellular CFU of B. melitensis being reduced by 80% at 48 h p.i. These findings demonstrate that pharmacological agents such as cisplatin may be considered to influence immune responses and apoptosis to help decrease Brucella-infected cell number.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cisplatin	Myeloperoxidase	Protein	Humans	Unknown	Inducer	Details
Cisplatin	Xanthine dehydrogenase/oxidase	Protein	Humans	Unknown	Inducer	Details