Opposing effects of estradiol and progesterone on the oxidative stress-induced production of chemokine and proinflammatory cytokines in murine peritoneal macrophages

Abstract

In inflammatory and oxidative liver injury, virus proteins and reactive oxygen species are involved in the regulation of proinflammatory cytokine production by macrophages. This study investigated the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stress-stimulated production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, macrophage inflammatory protein (MIP)-2, and macrophage chemotactic protein (MCP)-1 by peritoneal macrophages isolated from male and female mice. E2 inhibited the cytokine production of TNF-alpha, IL-1beta, MIP-2, and MCP-1 by the unstimulated macrophages from males and females, which was then further stimulated by progesterone. The exposure to hydrogen peroxide in the macrophages from both sexes induced the production of cytokine. The hydrogen peroxide-stimulated cytokine production was suppressed by E2 and enhanced by progesterone. The sex hormone effects on the unstimulated and stimulated macrophages were blocked by their receptor antagonists and showed no significant difference between male and female subjects. These findings suggest that E2 may play a favorable role in the course of persistent liver injury, by inhibiting proinflammatory cytokine production, which, in addition, progesterone may counteract the favorable E2 effects through their receptors.

Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

“…[55] In addition, E 2 inhibited the production of TNF-a by the unstimulated and hydrogen peroxide-stimulated macrophages from males and females. [56] Parallel to these findings, the present data demonstrate that elevated serum TNF-a levels of CRF rats are depressed by exogenous E 2 treatment, suggesting that E 2 -induced alleviation of CRF-induced oxidative damage involves the modulation of the synthesis of TNF-a.…”

Hepatoprotective effect of tamoxifen on steatosis and non-alcoholic steatohepatitis in mouse models

“…4). It has been reported that estrogen attenuates the expressions of TNFα and MCP-1via the estrogen receptor in female mice (Huang et al, 2008). Thus, these results indicated that TAM would exert a hepatoprotective effect against inflammation in the steatosis and NASH model mice.…”

Sex steroids as inflammatory regulators

“…Progesterone, meanwhile, was shown to limit the production of NO by LPSactivated alveolar macrophages [34] and bone marrow-derived macrophages (BMDM) activated with a combination of interferon (IFN)-␥ and LPS [35]. It also stimulated the secretion of TNF-␣, IL-1␤ and the chemokine macrophage inflammatory protein (MIP)-2 from unactivated peritoneal macrophages [36] while estradiol suppressed the production of these three inflammatory mediators [36]. In a mouse macrophage cell line, estradiol blocked LPS's induction of its own receptor (TLR4), and attenuated cell activation, as assessed morphologically [37].…”