Cisplatin primes murine peritoneal macrophages for enhanced expression of nitric oxide, proinflammatory cytokines, TLRs, transcription factors and activation of MAP kinases upon co-incubation with L929 cells
| Autor: | Puja Chauhan, Ajit Sodhi, Anju Shrivastava |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cytotoxicity
Immunologic MAP Kinase Kinase 4 MAP Kinase Signaling System Adipose tissue macrophages p38 mitogen-activated protein kinases Immunology Biology Nitric Oxide Proinflammatory cytokine Wortmannin Mice chemistry.chemical_compound medicine Animals Immunology and Allergy Cell Line Transformed MAPK14 Anthracenes Flavonoids Cisplatin Mice Inbred BALB C Kinase Hematology Macrophage Activation Coculture Techniques Toll-Like Receptor 2 Cell biology Androstadienes Toll-Like Receptor 4 chemistry Macrophages Peritoneal Myeloid-derived Suppressor Cell Cytokines Inflammation Mediators Signal Transduction medicine.drug |
| Zdroj: | Immunobiology. 214:197-209 |
| ISSN: | 0171-2985 |
| DOI: | 10.1016/j.imbio.2008.07.012 |
| Popis: | Cisplatin, a chemotherapeutic drug, may also act as a biological response modifier. Cisplatin (10mug/ml) treatment of macrophages for 24h activates them to produce enhanced amounts of nitric oxide (NO), ROI, proinflammatory cytokines and exhibit increased tumoricidal activity, which may or may not be contact mediated. In the present investigation, we report that the treatment of macrophages with cisplatin for a short period of 2h is sufficient to make them more receptive to interaction with tumor cells. Macrophages pretreated with cisplatin for 2h, and co-incubated with L929 cells, produced enhanced NO, TNF-alpha, IL-1beta, IL-12 and IFN-gamma. Production of NO, TNF-alpha, IL-1beta, IL-12 and IFN-gamma was maximum at 24h of co-incubation. Enhanced transcription of iNOS, TNF-alpha, IL-1beta, IL-12 and IFN-gamma genes in cisplatin-pretreated macrophages were observed between 12 and 24h of co-incubation with L929 cells. Cisplatin-treated macrophages on co-incubation with L929 cells also expressed enhanced transcription of Toll-like receptor (TLR)-2 and TLR-4 genes and their proteins. It is observed that cisplatin-pretreated macrophages on co-incubation with L929 cells showed activation of mitogen-activated protein (MAP) kinases and NF-kappaB. Pharmacological inhibitors like PD98059, SB202190 and wortmannin strongly inhibited the production of NO and proinflammatory cytokines suggesting the probable role of p42/44, p38 MAPK and PI3K in the above process. The c-Jun amino terminal kinase (JNK) inhibitor SP600125 was less effective in inhibiting the production of NO and proinflammatory cytokines. The data thus suggests that pretreatment of macrophages with cisplatin makes them biologically more responsive to interaction with L929 cells and become activated. |
| Databáze: | OpenAIRE |
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