Pulmonary phthalate exposure and asthma: Is PPAR a plausible mechanistic link?
2013 (English)In: EXCLI Journal, ISSN 1611-2156, E-ISSN 1611-2156, Vol. 12, 733-759 p.Article in journal (Refereed) Published
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 antiinflammatory 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.
Place, publisher, year, edition, pages
2013. Vol. 12, 733-759 p.
immunoglobulin E; peroxisome proliferator activated receptor alpha; phthalic acid; volatile organic compound, adipogenesis; adsorption kinetics; adverse outcome; ambient air; antiinflammatory activity; article; asthma; cell free system; chemical reaction kinetics; concentration response; disease exacerbation; environmental exposure; environmental parameters; enzyme regulation; genetic transfection; house dust; human; immunoglobulin production; in vitro study; in vivo study; ingestion; intracellular signaling; ligand binding; liver cell; liver clearance; liver metabolism; metabolism; molecular interaction; molecular mechanics; molecular model; molecular weight; nonhuman; particulate matter; pathogenesis; protein function; protein induction; protein interaction; receptor binding; respiratory tract allergy; respiratory tract inflammation; transactivation
Public Health, Global Health, Social Medicine and Epidemiology
IdentifiersURN: urn:nbn:se:kau:diva-43903ISI: 000323213400001ScopusID: 2-s2.0-84882703318OAI: oai:DiVA.org:kau-43903DiVA: diva2:945129