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. Author manuscript; available in PMC: 2013 Feb 15.
Published in final edited form as: J Immunol. 2012 Jan 6;188(4):1970–1980. doi: 10.4049/jimmunol.1102383

Figure 11.

Figure 11

MMP-1 and MMP-3 induce macrophage mPGES-1 expression: Role of TNF-α and EP4 receptor. Our data suggest that MMP-1 and MMP-3 selectively induce mPGES-1 expression, which is dependent on the release of TNF-α, activation of MAPKerk1/2 and induction of Egr-1 expression. Proteinase induced MMP-9 expression in macrophages was blocked by mPGES-1 silencing. Elevated mPGES-1 expression and PGE2 levels were regulated by a positive feedback loop that was dependent on the EP4 prostanoid receptor. Thus, in addition to inhibiting macrophage MMP-9 expression, EP4 antagonists emerge as potential therapeutic agents to reduce mPGES-1 expression and PGE2 levels in inflammatory or neoplastic settings.