Novel implications in the development of endometriosis: biphasic effect of macrophage activation on peritoneal tissue expression of tissue inhibitor of metalloproteinase-1.

Abstract

Elevated levels of activated macrophages are associated with endometriosis, but their role in the etiology of the disease is uncertain. The current study was undertaken to examine whether activated macrophages could modulate peritoneal tissue expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1), which may play a role in the development of endometriosis. Female mice were treated with the macrophage activator lipopolysaccharide (LPS), and peritoneum TIMP-1 mRNA was examined by Northern blot analysis. LPS induced a dose-dependent increase (P < 0.05) in TIMP-1 mRNA expression at levels of 1 microgram (70.0% +/- 5.8% greater than the control), 10 micrograms (83.0% +/- 12.0% greater than the control), and 25 micrograms (100.0% +/- 10.0% greater than the control). In contrast, the administration of 50 micrograms of LPS resulted in a decrease in TIMP-1 mRNA expression below baseline levels (18.0% +/- 6.0% less than the control values). Activated macrophages and/or their products modulate peritoneum TIMP-1 expression. These data suggest that, in addition to their phagocytotic role in the peritoneal cavity, these immune cells also may play a novel role in influencing the ability of the peritoneum to regulate tissue/cell invasion and in the development of endometriosis through TIMP-1 expression.