title: Pulmonary phthalate exposure and asthma - is PPAR a plausible mechanistic link?
abstract: Due to their extensive use as plasticisers in numerous consumer products, phthalates have become ubiquitous environmental contaminants. An increasing number of epidemiological studies suggest that exposure to phthalates may be associated with worsening or development of airway diseases. Peroxisome Proliferation Activated Receptors (PPAR)s, identified as important targets for phthalates in early studies in rodent liver, have been suggested as a possible mechanistic link. In this review we discuss the likelihood of an involvement of PPARs in asthma development and exacerbation due to pulmonary phthalate exposure. First, we go through the literature on indoor air levels of phthalates and pulmonary phthalate kinetics. These data are then used to estimate the pulmonary phthalate levels due to inhalation exposure. Secondly, the literature on phthalate-induced activation or modulation of PPARs is summarized. Based on these data, we discuss whether pulmonary phthalate exposure is likely to cause PPAR activation, and if this is a plausible mechanism for adverse effects of phthalates in the lung. It is concluded that the pulmonary concentrations of some phthalates may be sufficient to cause a direct activation of PPARs. Since PPARs mainly mediate anti-inflammatory effects in the lungs, a direct activation is not a likely molecular mechanism for adverse effects of phthalates. However, possible modulatory effects of phthalates on PPARs deserve further investigation, including partial antagonist effects and/or cross talk with other signalling pathways. Moreover other mechanisms, including interactions between phthalates and other receptors, could also contribute to possible adverse pulmonary effects of phthalates.
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Anette
authors.initials: A
authors.lastname: Kocbach Bølling
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
authors.affiliation: University of Karlstad, 651-88, Karlstad, Sweden.
authors.forename: Carl Gustaf
authors.initials: CG
authors.lastname: Bornehag
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Unni C
authors.initials: UC
authors.lastname: Nygaard
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Bertelsen
authors.affiliation: University of Karlstad, 651-88, Karlstad, Sweden.
authors.forename: Eewa
authors.initials: E
authors.lastname: Nånberg
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Johanna
authors.initials: J
authors.lastname: Bodin
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Amrit Kaur
authors.initials: AK
authors.lastname: Sakhi
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Thomsen
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Becher
keywords: Peroxisome Proliferation Activated Receptors; asthma; molecular mechanism; phthalates