Abstract |
Macrophage-activating lipopeptide-2 (MALP-2) is a potent inducer of proinflammatory cytokine secretion by macrophages, monocytes, and dendritic cells. MALP-2 was reported to be involved in natural killer (NK) cell activation and ensuing tumor rejection. However, the mechanism of MALP-2-mediated NK cell activation remained unclear. Therefore, we studied the effects of MALP-2 on cultured human NK cells. We found that MALP-2 had no direct effect on NK cells. Instead, MALP-2 acted on monocytes and triggered the release of different molecules such as interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-15, interferon gamma-induced protein (IP-10), and prostaglandin (PG)-E2. Our data show that monocyte-derived IP-10 could significantly induce NK cell cytotoxicity as long as the immunosuppression by PGE2 is specifically inhibited by cyclooxygenase (COX)-2 blockade. In summary, our results show that MALP-2-mediated stimulation of monocytes results in the production of several mediators which, depending on the prevailing conditions, affect the activity of NK cells in various ways. Hence, MALP-2 administration with concurrent blocking of COX-2 can be considered as a promising approach in MALP-2-based adjuvant tumor therapies.
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Authors | Christina Müller, Dejene M Tufa, Debanjana Chatterjee, Peter F Mühlradt, Reinhold E Schmidt, Roland Jacobs |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 64
Issue 9
Pg. 1175-84
(Sep 2015)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 26036909
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclooxygenase 2 Inhibitors
- Lipopeptides
- TLR2 protein, human
- TLR6 protein, human
- Toll-Like Receptor 2
- Toll-Like Receptor 6
- macrophage stimulatory lipopeptide 2
- Dinoprostone
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Topics |
- Cells, Cultured
- Cyclooxygenase 2 Inhibitors
(immunology, pharmacology)
- Dinoprostone
(antagonists & inhibitors, biosynthesis, immunology)
- Humans
- Killer Cells, Natural
(drug effects, immunology)
- Lipopeptides
(immunology, pharmacology)
- Monocytes
(drug effects, immunology)
- Signal Transduction
- Toll-Like Receptor 2
(agonists)
- Toll-Like Receptor 6
(agonists)
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