title: Induction of inflammatory mediators in human airway epithelial cells by lipid ozonation products.
abstract: We have proposed that exposure of epithelial cell membrane lipids in the lung (mainly phospholipids) to ozone will generate lipid ozonation products (LOP), which could be responsible for the proinflammatory effects of ozone. The ozonation of phosphocholine, the principal membrane phospholipid, produces a limited number of LOP, including hydroxyhydroperoxides and aldehydes. We now report that exposure of cultured human bronchial epithelial cells to the ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) product, 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine (PC-ALD), a phospholipase A(2) (PLA(2))-stimulatory LOP, resulted in a 113 +/- 11% increase in the amounts of tritiated platelet-activating factor ((3)H-PAF) released apically. (3)H-PAF release was also induced by 1-hydroxy-1-hydroperoxynonane of ozonized POPC (HHP-C9), a phospholipase C (PLC)- stimulatory LOP (134 +/- 40% increase in (3)H-PAF). PC-ALD at 10 microM, but not HHP-C9, induced a 127 +/- 24% increase in prostaglandin E(2) (PGE(2)) release (n = 6, p < 0.05). In contrast, HHP-C9, but not PC-ALD, induced interleukin (IL)-6 release (178 +/- 23% increase, n = 6, p < 0.05) and IL-8 release (101 +/- 23% increase, n = 8, p < 0. 05). These results suggest that LOP-dependent release of proinflammatory mediators may play an important role in the early inflammatory response seen during exposure to ozone.
authors.affiliation: Section of Pulmonary Diseases, Critical Care and Environmental Medicine, and Tulane/Xavier Center for Bioenvironmental Research, Tulane University Medical Center, New Orleans, LA 70112, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Kafoury
authors.forename: W A
authors.initials: WA
authors.lastname: Pryor
authors.forename: G L
authors.initials: GL
authors.lastname: Squadrito
authors.forename: M G
authors.initials: MG
authors.lastname: Salgo
authors.forename: X
authors.initials: X
authors.lastname: Zou
authors.forename: M
authors.initials: M
authors.lastname: Friedman
mesh_terms: D000473:Alkanes / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008563:Membrane Lipids / Q000378:metabolism*; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D010545:Peroxides / Q000633:toxicity*; D010713:Phosphatidylcholines / Q000633:toxicity*; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: C405904:1-hydroxy-1-hydroperoxynonane; D000473:Alkanes; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008563:Membrane Lipids; D010083:Oxidants, Photochemical; D010545:Peroxides; D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D010126:Ozone; D010741:Phospholipases A; D010738:Type C Phospholipases; D015232:Dinoprostone; C028694:1-palmitoyl-2-oleoylphosphatidylcholine