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Prostaglandin E2 does not inhibit tumoricidal activity of mouse macrophages against adherent tumor cells
1Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Abstract:
We determined whether endogenously produced PGE2 can down-regulate the tumoricidal properties of macrophages by a negative feedback mechanism. Peritoneal exudate macrophages or resident peritoneal macrophages of mice were incubated in medium (control) or in medium containing IFN-gamma and LPS. Activated macrophages were highly tumoricidal against syngeneic melanoma cells and secreted high levels of PGE2. Treatment with indomethacin or diclofenac sodium (voltaren) completely inhibited the production and secretion of PGE2 but not the tumoricidal activity of activated macrophages measured either immediately after activation or 1 to 3 days thereafter. Finally, the addition of exogenous PGE2 did not alter the ability of peritoneal exudate macrophages to respond to IFN-gamma or of LPS to produce high levels of tumor cell lysis. Collectively, these results show that PGE2 produced by activated macrophages is not a down-regulator of their tumoricidal activity against adherent tumor cells.
Insights
This study investigated if prostaglandin E2 (PGE2) from macrophages reduces their tumor-killing ability. Results show that PGE2 does not inhibit macrophage tumoricidal activity, even when its production is blocked.
Area of Science:
- Immunology
- Cancer Biology
- Prostaglandin Research
Background:
- Macrophages play a crucial role in anti-tumor immunity.
- Prostaglandin E2 (PGE2) is a molecule produced by activated macrophages.
- The potential negative feedback role of PGE2 on macrophage function is not fully understood.
Purpose of the Study:
- To determine if endogenously produced PGE2 down-regulates the tumoricidal properties of activated macrophages.
- To investigate the mechanism of PGE2 regulation on macrophage-mediated tumor cell lysis.
Main Methods:
- Murine peritoneal exudate macrophages and resident peritoneal macrophages were activated with IFN-gamma and LPS.
- Macrophage tumoricidal activity against syngeneic melanoma cells was assessed.
- PGE2 production was inhibited using indomethacin or diclofenac sodium, and exogenous PGE2 was added to assess its effects.
Main Results:
- Activated macrophages exhibited significant tumoricidal activity and secreted high levels of PGE2.
- Inhibition of PGE2 production did not affect the immediate or delayed tumoricidal activity of activated macrophages.
- Addition of exogenous PGE2 did not impair the ability of macrophages to be activated or to lyse tumor cells.
Conclusions:
- Endogenously produced PGE2 does not act as a negative feedback regulator of macrophage tumoricidal activity.
- The study demonstrates that PGE2 does not inhibit the ability of activated macrophages to kill adherent tumor cells.