The phospholipase D pathway mediates the inflammatory response ofthe retinal pigment epithelium

MATEOS, M.V.; KAMERBEEK, C.; GIUSTO, N.M.; SALVADOR, G.A. AUTOR CORRESP.

INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELLULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2014 vol. 55 p. 119 - 128

1357-2725

tThe retinal pigment epithelium (RPE) plays an important immunological role in the retina and it isinvolved in many ocular inflammatory diseases that may end in loss of vision and blindness. In thiswork the role of phospholipase D (PLD) classical isoforms, PLD1 and PLD2, in the inflammatory responseof human RPE cells (ARPE-19) was studied.ARPE-19 cells exposed to lipopolysaccharide (LPS, 10 g/ml) displayed increased levels of NO production and diminished mitochondrial function after 48 h of incubation. Furthermore, 24 h LPS treatmentstrongly induced cyclooxygenase-2 (COX-2) expression and activation of extracellular signal-regulatedkinase (ERK1/2). EGFP-PLDs showed the typical subcellular localization, perinuclear for PLD1 and plasmamembrane for PLD2. LPS increased PLD activity by 90% with respect to the control. The presence ofPLD1 inhibitor (EVJ 0.15 M) or PLD2 inhibitor (APV 0.5 M) reduced LPS-induced COX-2 induction butonly PLD2 inhibition reduced ERK1/2 activation. Mitochondrial function was restored after inhibition ofPLD2 and ERK1/2. These findings evidence the participation of PLD2 as a promoter of RPE inflammatoryresponse through ERK1/2 and COX-2 regulation. Our results demonstrate for the first time distinctive roles of PLD isoforms in pathological conditions in RPE.