The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-alpha production

Abstract

The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-alpha and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17 beta-estradiol on LPS-induced macrophage TNF-alpha and NO production. Results showed that: ( a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-alpha, but not NO production; (b) estradiol level gradually increased following ovariectomy;