title: Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production.
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.
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Mustafa Kemal University, Hatay 31040, Turkey. serdogan@mku.edu.tr
authors.forename: Suat
authors.initials: S
authors.lastname: Erdogan
authors.forename: Eda
authors.initials: E
authors.lastname: Tosyali
authors.forename: Vesile
authors.initials: V
authors.lastname: Duzguner
authors.forename: Altug
authors.initials: A
authors.lastname: Kucukgul
authors.forename: Ozkan
authors.initials: O
authors.lastname: Aslantas
authors.forename: Sefa
authors.initials: S
authors.lastname: Celik
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D017347:Brucella melitensis / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D016877:Oxidants / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D016877:Oxidants; D002945:Cisplatin