|Title||Inflammatory effects of phthalates in neonatal neutrophils|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Vetrano A.M, Laskin D.L, Archer F., Syed K., Gray J.P, Laskin J.D, Nwebube N., Weinberger B.|
|Journal||Pediatr ResPediatr Res|
|ISBN Number||1530-0447 (Electronic)<br/>0031-3998 (Linking)|
|Keywords||*Neutrophils/drug effects/immunology, Adult, Apoptosis/drug effects, Chemotaxis/drug effects, Diethylhexyl Phthalate/analogs & derivatives/metabolism/pharmacology, Humans, Hydrogen Peroxide/metabolism, Infant, Newborn, Inflammation/*chemically induced, Oxidants/metabolism, Phthalic Acids/*pharmacology, Plasticizers/metabolism/pharmacology, PPAR gamma/metabolism, Signal Transduction/drug effects|
Hospitalized infants are exposed to numerous devices containing the plasticizer di-(2-ethylhexyl) phthalate. Urinary levels of the phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are markedly elevated in premature infants. Phthalates inactivate peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear transcription factor that mediates the resolution of inflammation, a process impaired in neonates. We speculate that this increases their susceptibility to MEHP, and this was analyzed. MEHP inhibited neutrophil apoptosis; neonatal cells were more sensitive than adult cells. In neonatal, but not in adult neutrophils, MEHP also inhibited chemotaxis, stimulated oxidative metabolism, and up-regulated expression of NADPH oxidase-1. In both adult and neonatal neutrophils, MEHP stimulated IL-1beta and VEGF production, whereas IL-8 production was stimulated only in adult cells. In contrast, MEHP-inhibited production of MIP-1beta by adult cells, and Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) by neonatal neutrophils. The effects of MEHP on apoptosis and oxidative metabolism in neonatal cells were reversed by the PPAR-gamma agonist, troglitazone. Whereas troglitazone had no effect on MEHP-induced alterations in inflammatory protein or chemokine production, constitutive IL-8 and MIP-1beta production was reduced in adult neutrophils, and RANTES and MIP-1beta in neonatal cells. These findings suggest that neonatal neutrophils are more sensitive to phthalate-mediated inhibition of PPAR-gamma, which may be related to decreased anti-inflammatory signaling.