Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Induction of inflammatory mediators in human airway epithelial cells by lipid ozonation products. 1058 9

Ozone (O(3)) is a major component of smog and an inhaled toxicant to the lung. O(3) rapidly reacts with the airway epithelial cell membrane phospholipids to generate lipid ozonation products (LOP). 1-Hydroxy-1-hydroperoxynonane (HHP-C9) is an important LOP, produced from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatidylcholine. This LOP, at a biologically relevant concentration (100 microM), increases the activity of phospholipase C, nuclear factors-kappaB (NF-kappaB), and interleukin-6 (NF-IL-6) and the expression of the inflammatory gene, interleukin-8 (IL-8) in a cultured human bronchial epithelial cell line (BEAS-2B). The signaling pathways of ozone and its biologically-active products are as yet undefined. In the present study, we report that the HHP LOP, HHP-C9 (100 microM x 4 h), activated the expression of IL-8 (218 +/- 26% increase over control, n = 4, P < 0.01) through an apparent interaction between the two transcription factors, NF-kappaB and NF-IL-6. Transfection studies using luciferase reporter assays demonstrated that HHP-C9 induced a significant increase in NF-kappaB-DNA binding activity (37 +/- 7% increase over control, n = 6, P < 0.05). Inhibition of NF-kappaB showed a statistically significant but modest decrease in IL-8 release, which suggested a role for another transcription factor, NF-IL-6. Exposure of BEAS-2B cells to HHP-C9 induced a significant increase in the DNA binding activity of NF-IL-6 (45 +/- 11% increase over control, n = 6, P < 0.05). The results of the present study indicate that NF-IL-6 interacts with NF-kappaB in regulating the expression of IL-8 in cultured human airway epithelial cells exposed to LOP, the biological products of ozone in the lung.
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PMID:Activation of transcription factor IL-6 (NF-IL-6) and nuclear factor-kappaB (NF-kappaB) by lipid ozonation products is crucial to interleukin-8 gene expression in human airway epithelial cells. 1736 69