The TLR-2/TLR-6 agonist macrophage-activating lipopeptide-2 augments human NK cell cytotoxicity when PGE2 production by monocytes is inhibited by a COX-2 blocker

Christina Müller, Dejene M Tufa, Debanjana Chatterjee, Peter F. Mühlradt, Reinhold E. Schmidt, Roland Jacobs

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1175-1184
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume64
Issue number9
DOIs
StatePublished - Sep 21 2015

Keywords

  • COX-2 upregulation
  • IP-10
  • MALP-2
  • Monocytes
  • NK cell activation
  • PGE2

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