Various secretory phospholipase A2 enzymes are expressed in rheumatoid arthritis and augment prostaglandin production in cultured synovial cells.
Although group IIA secretory phospholipase A2 (sPLA2-IIA) is known to be abundantly present in the joints of patients with rheumatoid arthritis (RA), expression of other sPLA2s in this disease has remained unknown. In this study, we examined the expression and localization of six sPLA2s (groups IIA, IID, IIE, IIF, V and X) in human RA. Immunohistochemistry of RA sections revealed that sPLA2-IIA was generally located in synovial lining and sublining cells and cartilage chondrocytes, sPLA2-IID in lymph follicles and capillary endothelium, sPLA2-IIE in vascular smooth muscle cells, and sPLA2-V in interstitial fibroblasts. Expression levels of these group II subfamily sPLA2s appeared to be higher in severe RA than in inactive RA. sPLA2-X was detected in synovial lining cells and interstitial fibers in both active and inactive RA sections. Expression of sPLA2-IIF was partially positive, yet its correlation with disease states was unclear. Expression of sPLA2 transcripts was also evident in cultured normal human synoviocytes, in which sPLA2-IIA and -V were induced by interleukin-1 and sPLA2-X was expressed constitutively. Adenovirus-mediated expression of sPLA2s in cultured synoviocytes resulted in increased prostaglandin E2 production at low ng x mL(-1) concentrations. Thus, multiple sPLA2s are expressed in human RA, in which they may play a role in the augmentation of arachidonate metabolism or exhibit other cell type-specific functions.
Masuda
Seiko
S
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Murakami
Makoto
M
Komiyama
Kazuo
K
Ishihara
Motoko
M
Ishikawa
Yukio
Y
Ishii
Toshiharu
T
Kudo
Ichiro
I
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone