Phospholipase D1 Is Up-Regulated in the Retina of Lewis Rats with Experimental Autoimmune Uveoretinitis

Abstract

To investigate whether phospholipase D1 (PLD1) is involved in autoimmune damage to the eyes, we used Western blotting and immunohistochemistry to examine the expression and distribution of PLD1 in the retinas of Lewis rats with experimental autoimmune uveoretinitis (EAU). Western blot analysis showed that the level of expression of PLD1 was significantly increased in EAU-affected retinas compared to that of control. Immunohistochemical analysis showed that ganglion cells and Muller cells, which express PLD1 weakly in the normal retina, showed increased expression of PLD1 in EAU-affected retinas; some ED1-immunopositive cells were also immunopositive for PLD1 in lesions at post-immunization days 14 and 21. These results suggest that the increased expression of PLD1 in inflammatory cells exacerbates an autoimmune response in EAU, while its expression in ganglion cells limits cell loss by activation of survival factors in eyes with autoimmune injury.

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

“…These findings suggest that PLD isoform inhibition has anti‐inflammatory effects in HPDLCs. These results are consistent with those of previous in vivo and in vitro studies 19‐22,24,26 …”

“…In the present study, both PLD1 and PLD2 mRNA are upregulated in vivo in patients with periodontitis, as well as in vitro in HPDLCs stimulated with nicotine and LPS. This upregulation of PLD1 and PLD2 also has been observed in an animal model of uveoretinitis, 20 injured spinal cords, 21 myocardial ischemia/reperfusion, 41 and septic shock 22 and in vitro LPS‐stimulated RAW 264.7 cells 28 . 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 .…”

“…PLD1 has been reported to be upregulated in experimental autoimmune uveoretinitis, 20 the injured spinal cords of rats, 21 and macrophages and astrocytes in the cryoinjured cerebral cortices of rats 22 . In addition, the protein level of PLD1, but not PLD2, is upregulated selectively in IL‐15‐induced rheumatoid synovial fibroblasts, 23 IL‐1β‐stimulated synoviocytes, and synovia from patients with rheumatoid arthritis (RA) 24 .…”

Blood-retina barrier dysfunction in experimental autoimmune uveitis: the pathogenesis and therapeutic targets

“…Bovine retinal homogenate including a variety of retinal antigens is associated with the generation of uveitogenic autoimmune T cells in Lewis rats [ 11 ]. The susceptibility of inbred rat strains and pathogenic peptides has been analyzed in Lewis rats [ 10 , 12 ].…”