Tài liệu Báo cáo khoa học: Various secretory phospholipase A2 enzymes are expressed in rheumatoid

Various secretory phospholipase A2 enzymes are

expressed in rheumatoid arthritis and augment

prostaglandin production in cultured synovial cells

Seiko Masuda1

, Makoto Murakami1

, Kazuo Komiyama2

, Motoko Ishihara3

, Yukio Ishikawa3

,

Toshiharu Ishii3 and Ichiro Kudo1

1 Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan

2 Department of Pathology, Division of Immunology and Patho-Biology at Dental Research Center, Nihon University School of Dentistry,

Tokyo, Japan

3 Department of Pathology, Toho University School of Medicine, Tokyo, Japan

Secretory phospholipase A2 (sPLA2) is a group of

disulfide-rich, low molecular mass, lipolytic enzymes

with a His-Asp catalytic dyad [1,2]. To date, 10 sPLA2

enzymes (IB, IIA, IIC, IID, IIE, IIF, III, V, X and

XIIA) have been identified in mammals. Of these

enzymes, sPLA2s in the I⁄II⁄ V ⁄X branch share many

structural characteristics and are thought to have

diverged from a common ancestor gene by successive

gene duplication events. The expression of individual

sPLA2s is tissue specific and often stimulus inducible

[3–15], leading to the proposal that they may play

tissue-specific functions during inflammation, tissue

Keywords

immunohistochemistry; phospholipase A2;

prostaglandin; rheumatoid arthritis; synovial

cell

Correspondence

M. Murakami, Department of Health

Chemistry, School of Pharmaceutical

Sciences, Showa University, 1-5-8

Hatanodai, Shinagawa-ku, Tokyo 142-8555,

Japan

Fax: +81 3 37848245

Tel: +81 3 37848197

E-mail: [email protected]

(Received 8 May 2004, revised 26 October

2004, accepted 17 November 2004)

doi:10.1111/j.1742-4658.2004.04489.x

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. Immunohistochemis￾try of RA sections revealed that sPLA2-IIA was generally located in syn￾ovial 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 intersti￾tial 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 nor￾mal 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 ngÆmL)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.

Abbreviations

AA, arachidonic acid; COX, cyclooxygenase; cPGES, cytosolic prostaglandin E synthase; cPLA2, cytosolic PLA2; ER, endoplasmic reticulum;

HSPG, heparan sulfate proteoglycan; IFN-c, interferon-c; IL-1b, interleukin-1b; mPGES, membrane-bound prostaglandin E synthase; NaCl ⁄ Pi

,

phosphate-buffered saline; PtdCho, phosphatidylcholine; PG, prostaglandin; RA, rheumatoid arthritis; sPLA2, secretory phospholipase A2;

TNFa, tumor necrosis factor a; VSMC, vascular smooth muscle cells.

FEBS Journal 272 (2005) 655–672 ª 2005 FEBS 655