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

Expression of Phospholipase D in Periodontitis and Its Role in the Inflammatory and Osteoclastic Response by Nicotine‐ and Lipopolysaccharide‐Stimulated Human Periodontal Ligament Cells

“…41 In addition, PLD1 and PLD2 are not downregulated by LPS in RPE cells in the ARPE-19 cell line. 27 The results showed that proinflammatory cytokines (IL-1b and TNF-a) had strong PLD1-and PLD2-inducing effects, whereas immune cytokines (IL-6 and IFN-g) had weak effects, which suggests that the upregulation of the PLD isoforms may be partially explained by a total increase in the inflammatory response.…”

“…However, PLD1, but not PLD2, is upregulated selectively in IL‐15‐induced rheumatoid synovial fibroblasts, 23 IL‐1β‐stimulated synoviocytes, synovia from patients with RA, 24 and TNF‐α‐stimulated human monocytes 41 . In addition, PLD1 and PLD2 are not downregulated by LPS in RPE cells in the ARPE‐19 cell line 27 . The results showed that proinflammatory cytokines (IL‐1β and TNF‐α) had strong PLD1‐ and PLD2‐inducing effects, whereas immune cytokines (IL‐6 and IFN‐γ) had weak effects, which suggests that the upregulation of the PLD isoforms may be partially explained by a total increase in the inflammatory response.…”

“…To the best of the authors’ knowledge, this is the first work demonstrating that these PLD inhibitors are able to modulate the expression of PLD1 and PLD2. EVJ and APV were shown to reduce LPS‐induced COX‐2 induction in human RPE cells in vitro 27 and to block iron‐induced oxidative stress‐induced diacylglycerol generation in synaptic endings in an in vivo rat model 44 . However, overexpression of PLD2, but not PLD1, increases LPS‐induced NO synthesis and iNOS expression, and knockdown of PLD2 using PLD2 siRNA completely abolishes iNOS expression and NO synthesis in RAW 264.7 cells, suggesting that LPS upregulates NO synthesis specifically through PLD2 28 .…”

“…However, the role of PLD2 in the inflammatory response remains unclear. Inhibition of PLD2 by small molecules or siRNA reduces COX‐2 induction by LPS in human retinal pigment epithelium (RPE) cells 27 and RAW 264.7 cells 28 . In contrast, recombinant human PLD2 suppresses the chronic inflammatory reaction in a guinea pig asthma model 29 .…”

Wogonin protects human retinal pigment epithelium cells from LPS-induced barrier dysfunction and inflammatory responses by regulating the TLR4/NF-κB signaling pathway

“…Lipopolysaccharide (LPS), also known as endotoxin, is the major cell wall constituent of gram-negative bacteria, and functions as a microglia activator via induction of TLR4 (25). In vitro assays have demonstrated that LPS induces inflammation in RPE, followed by subsequent destruction of the outer BRB (25,26). Therefore, cultured ARPE-19 cells were exposed to LPS to induce inflammation.…”