Abstract
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-γ (PPAR-γ), 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-1β and VEGF production, whereas IL-8 production was stimulated only in adult cells. In contrast, MEHP-inhibited production of MIP-1β 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-γ agonist, troglitazone. Whereas troglitazone had no effect on MEHP-induced alterations in inflammatory protein or chemokine production, constitutive IL-8 and MIP-1β production was reduced in adult neutrophils, and RANTES and MIP-1β in neonatal cells. These findings suggest that neonatal neutrophils are more sensitive to phthalate-mediated inhibition of PPAR-γ, which may be related to decreased anti-inflammatory signaling.
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Abbreviations
- DEHP:
-
di-(2-ethylhexyl) phthalate
- fMLP:
-
N-formyl-methionyl-leucyl-phenylalanine
- MEHP:
-
mono-(2-ethylhexyl) phthalate
- NOX1:
-
NADPH oxidase-1
- PPAR-γ:
-
peroxisome proliferator-activated receptor-γ
- PVC:
-
polyvinyl chloride
- TgT:
-
troglitazone
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Supported by National Institutes of Health grants HD042036, HD058019, GM034310, ES004738, ES005022, CA100994, CA132624, and AR055073.
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Vetrano, A., Laskin, D., Archer, F. et al. Inflammatory Effects of Phthalates in Neonatal Neutrophils. Pediatr Res 68, 134–139 (2010). https://doi.org/10.1203/PDR.0b013e3181e5c1f7
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DOI: https://doi.org/10.1203/PDR.0b013e3181e5c1f7
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