Cytosolic Phospholipase A2 Group IVα but Not Secreted Phospholipase A2 Group IIA, V, or X Induces Interleukin-8 and Cyclooxygenase-2 Gene and Protein Expression through Peroxisome Proliferator-activated Receptors γ 1 and 2 in Human Lung Cells

Abstract

It has been reported that interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) expression is regulated by peroxisome proliferator-activated receptor (PPAR)-␥ synthetic ligands. We have shown previously that cytosolic phospholipase A 2 (cPLA 2 ) is able to activate gene expression through PPAR-␥ response elements (Pawlic-

Low Molecular Weight Hyaluronan Activates Cytosolic Phospholipase A2α and Eicosanoid Production in Monocytes and Macrophages

“…HA-induced COX2 expression was TLR4/ MYD88-dependent in our model (Fig. 8, B-D), which raises the possibility of its cPLA 2 ␣ dependence, as we have shown previously in A549 cells (25). Currently, a preclinical evaluation study of a cPLA 2 ␣ inhibitor in asthma treatment has been published, showing promising results using various in vitro and in vivo approaches (78).…”

“…AA is the precursor of leukotrienes, prostaglandins, hydroxyeicosatetraenoic acids, thromboxanes, and lipoxins (22,23). cPLA 2 ␣ and its downstream metabolites can also directly modulate cellular function by altering intracellular transport (24) and regulating gene transcription (25,26). In experimental models of asthma (27), pulmonary fibrosis (28), ARDS (29), multiple sclerosis (30), and rheumatoid arthritis (31), cPLA 2 ␣ knock-out mice have reduced symptoms compared with wild-type mice (32).…”

2,2′,4,4′-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-κB

“…Activation of PLA 2 contributed to upregulation of COX-2 in murine macrophages and human lung cells (Balsinde et al 1999;Pawliczak et al 2002Pawliczak et al ,2004. Furthermore, free AA activates a variety of proteins involved in the regulation of COX-2 expression, including p38 MAP kinase (Hii et al 1998), peroxisome proliferator-activated receptor γ (Pawliczak et al 2002(Pawliczak et al , 2004 and phosphatidyl inositol-3-kinase (Monick et al 2002).…”

“…Furthermore, free AA activates a variety of proteins involved in the regulation of COX-2 expression, including p38 MAP kinase (Hii et al 1998), peroxisome proliferator-activated receptor γ (Pawliczak et al 2002(Pawliczak et al , 2004 and phosphatidyl inositol-3-kinase (Monick et al 2002). Interestingly, expression of COX-2 was decreased in brains of PLA 2 -deficient mice relative to wild type mice (Bosetti and Weerasinghe, 2003).…”

“…A number of shared or convergent pathways have been described that are involved in transcriptional regulation of COX-2 in response to inflammatory mediators, among which are NF-κB (Ghosh et al 1998) and elements of the mitogen-activated protein (MAP) kinase cascades (Dean et al 1999;Lasa et al 2000;Moon and Pestka, 2002;Steer et al 2006;Su and Karin, 1996). In addition, reactive oxygen species (ROS; Amma et al 2005) and activated phospholipase A 2 (PLA 2 ) and its product, free arachidonic acid (AA; Pawliczak et al 2004) have been implicated in the upregulation of COX-2 in various cell systems. Given the observation that PCBs increase COX-2 expression (Bezdecny et al 2005), it was of interest to determine the signal transduction pathways involved in this alteration.…”