Identification of a novel target for the action of endocrine disrupting chemicals: inhibitory effect of methylparaben on human neutrophil functions

Abstract

This study was conducted to verify a hypothesis that immune cells are a target for the action of endocrine disrupting chemicals (EDCs) by investigating whether methylparaben (MeP) modulates human neutrophil functions. Neutrophils isolated from 15 donor samples were studied. Cells were incubated in the presence of increasing MeP concentrations (0.06, 0.8, 10, and 20 μM). The cytotoxic effect of MeP on neutrophils was evaluated by the MTT test. The ability of the neutrophils for chemotaxis, phagocytosis, NADPH oxidase activity, and superoxide anion generation was assessed in Boyden's chamber, Park's method with latex, the NBT test, and the cytochrome C reduction test, respectively. The total nitric oxide (NO) concentration was measured by the Griess reaction. There was no observable cytotoxic effect of MeP on human neutrophils. MeP (10 and 20 μM) exposure decreased neutrophilic ability for the tested functions, except for NO production. In neutrophils incubated with MeP (0.8 μM as well as 0.06 and 0.8 μM, respectively), we observed a decreased activity of NADPH oxidase as well as decreased generation of superoxide anion. Our results suggest a suppressive effect of MeP on the tested functions of human neutrophils, which confirms that immune cells are vulnerable to EDC action. Therefore, the disturbance of neutrophils' oxygen-dependent phagocytic function as a result of exposure to environmental doses of MeP action could lead to impairment of innate immune responses in humans exposed to xenoestrogens.

Keywords: Endocrine disrupting chemicals; Endocrine disruptors; Methylparaben; Neutrophil; Oxidative burst; Parabens; Xenoestrogen.