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 A₂ (PLA₂)-stimulatory LOP, resulted in a 113 ± 11% increase in the amounts of tritiated platelet-activating factor (³H-PAF) released apically. ³H-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 ³H-PAF). PC-ALD at 10 μ M, but not HHP-C9, induced a 127 ± 24% increase in prostaglandin E₂ (PGE₂) 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. Kafoury RM, Pryor WA, Squadrito GL, Salgo MG, Zou X, Friedman M. Induction of inflammatory mediators in human airway epithelial cells by lipid ozonation products.