Gelatinase expression and activity in the synovium and skin of patients with erosive psoriatic arthritis.
OBJECTIVE
Matrix metalloproteinases (MMP), especially the gelatinases (MMP2, MMP9), have been implicated in several features of inflammatory arthritis including angiogenesis and bone erosions. We examined the expression and activity of the gelatinases and their regulators in psoriatic skin and synovium using tissue immunohistochemistry and a sensitive tissue based zymographic technique.


METHODS
Lesional and perilesional skin biopsies and synovial samples obtained by closed needle biopsy from 15 patients with erosive psoriatic arthritis (PsA) were analyzed by immunohistochemistry for the expression of the gelatinases and their regulators, tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, TIMP-2) and membrane type metalloproteinases (MTI-MMP. MT2-MMP), using immunohistochemistry. Synovial tissue from 8 patients with erosive rheumatoid arthritis (RA) was used as a comparison. MMP tissue expression was quantified by 2 blinded independent observers. Immunohistochemical data are reported as the mean percentage positive cells per total nucleated cells in 10 high power fields +/- SD. Functional activity of the gelatinases was measured using a sensitive tissue based zymography technique and corrected for protein content. Zymography data are presented as ng/mg +/- SE.


RESULTS
MMP expression was greater in the synovial lining layer (LL) than in the synovial sublining layer (SL) in both PsA and RA tissue for most MMP except collagenase I (MMPI), which was equally distributed between the LL and SL. Expression of MMP or their regulators did not differ between PsA synovial membrane (SM) and RA SM in LL. Moreover, although latent gelatinase A (MMP2) staining in PsA SM was equivalent to RA SM, increased gelatinase A activity was found in PsA SM over RA SM using zymography L82.4 (SD 62.8) vs 10.1 (SD 1.7); p = 0.02]. Compared to PsA SM, lesional skin had lower levels of MT1-MMP (MMP14) (1.4 +/- 1.7 vs 15.7 +/- 8.4; p = 0.009) and MT2-MMP (MMP15) (12.1 +/- 8.7 vs 21.6 +/- 9.9; p = 0.001).


CONCLUSIONS
We characterized the expression and activity of gelatinases in PsA and demonstrate that gelatinase activity in SM of PsA patients with erosive disease is comparable to if not greater than that in RA synovium.
Hitchon
Carol A
CA
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Danning
Carol L
CL
Illei
Gabor G
GG
El-Gabalawy
Hani S
HS
Boumpas
Dimitrios T
DT
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018450:Disease Progression; D005260:Female; D018093:Gelatinases / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053511:Matrix Metalloproteinase 14; D053517:Matrix Metalloproteinase 15; D020778:Matrix Metalloproteinase 2 / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D013583:Synovial Membrane / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C507098:MMP15 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D053517:Matrix Metalloproteinase 15; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14