Cytosolic phospholipase A2-driven PGE2 synthesis within unsaturated fatty acids-induced lipid bodies of epithelial cells.
Cytoplasmic lipid bodies (also known as lipid droplets) are intracellular deposits of arachidonic acid (AA), which can be metabolized for eicosanoid generation. PGE2 is a major AA metabolite produced by epithelial cells and can modulate restoration of epithelium homeostasis after injury. We studied lipid body biogenesis and their role in AA metabolic pathway in an epithelial cell line derived from normal rat intestinal epithelium, IEC-6 cells. Lipid bodies were virtually absent in confluent IEC-6 cells. Stimulation of confluent IEC-6 cells with unsaturated fatty acids, including AA or oleic acid (OA), induced rapid lipid body assembly that was independent on its metabolism to PGE(2), but dependent on G-coupled receptor-driven signaling through p38, PKC, and PI3 K. Newly formed lipid bodies compartmentalized cytosolic phospholipase (cPL)A(2)-alpha, while facilitated AA mobilization and synthesis of PGE(2) within epithelial cells. Thus, both lipid body-related events, including highly regulated biogenesis and functional assembly of cPLA (2)-alpha-driven enhanced AA mobilization and PGE(2)production, may have key roles in epithelial cell-driven inflammatory functions, and may represent relevant therapeutic targets of epithelial pathologies.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Luciana S
LS
Moreira
Bruno
B
Piva
Luciana B
LB
Gentile
Fabio P
FP
Mesquita-Santos
Heloisa
H
D'Avila
Clarissa M
CM
Maya-Monteiro
Patricia T
PT
Bozza
Christianne
C
Bandeira-Melo
Bruno L
BL
Diaz
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000166:cytology; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D019301:Oleic Acid / Q000494:pharmacology*; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008055:Lipids; D016718:Arachidonic Acid; D019301:Oleic Acid; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D054510:Phospholipases A2, Cytosolic; D015232:Dinoprostone