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International Immunology Advance Access originally published online on April 19, 2007
International Immunology 2007 19(5):635-643; doi:10.1093/intimm/dxm029
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Differential expression of Toll-like receptors in murine peritoneal macrophages in vitro on treatment with cisplatin

Shikha Tarang, Ajit Sodhi and Puja Chauhan

School of Biotechnology, Banaras Hindu University, Varanasi 221005, India

Corresponding to: A. Sodhi; E-mail: ajit.sodhi{at}lycos.com

In the present study, we have investigated the differential expression of Toll-like receptors [(TLRs) 1–9] in murine peritoneal macrophages in vitro, on treatment with cis-diaminedichloroplatinum (II) (cisplatin). It is demonstrated that cisplatin induces the expression of TLRs and is a potent activator of Toll-signaling pathway. The enhanced expression of TLR2, -3, -4, -5, -6, -7, -8 and -9 is observed at different time intervals after 5 µg ml–1 cisplatin treatment. The expression of downstream signaling molecules of TLR-signaling pathway—myeloid differentiation factor 88, IRAK1, tumor necrosis factor receptor-associated factor 6 and transcription factors IRF3 and nuclear factor-{kappa}B (NF-{kappa}B)—has also been investigated. The expression of TLR2, -3, -4 and -9 was down-regulated in cisplatin-treated macrophages in the presence of inhibitors of mitogen-activated protein kinases and NF-{kappa}B pathways, suggesting a role of these pathways in cisplatin-induced TLR expression. It is also observed that pre-treatment of macrophages with cisplatin and subsequent incubation with TLR ligands significantly enhanced the production of pro-inflammatory cytokines (tumor necrosis factor-{alpha}, IFN-{gamma}, IL-1ß and IL-12) and iNOS expression in macrophages. The data suggest that treatment of macrophages with cisplatin renders them more susceptible to subsequent induction of pro-inflammatory cytokines and iNOS expression by different TLR ligands. It is proposed that the pharmacological reagents like cisplatin can be used to manipulate the innate immune responses, which may be effectively used for the development of novel therapeutic approaches.

Keywords: cisplatin, macrophage activation, Toll-like receptors


Transmitting editor: A. Falus

Received 14 December 2006, accepted 23 February 2007.


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