MMP expression in rheumatoid inflammation: the rs11568818 polymorphism is associated with MMP-7 expression at an extra-articular site.
Matrix metalloproteinases (MMPs) contribute to the joint damage in rheumatoid arthritis (RA). Less is known of the involvement of MMPs at extra-articular sites of rheumatoid inflammation. We assessed the relative contribution from MMP-1, MMP-3, MMP-7 and MMP-12 to joint and extra-articular tissue destruction and inflammation by comparing gene expression in joint synovia and subcutaneous rheumatoid nodules from RA patients. Expression of MMP-1 and MMP-3 predominated in synovia, whereas MMP-12 expression was significantly higher in rheumatoid nodules. Markedly higher MMP-7 expression distinguished a subgroup of nodules that featured infiltrating monocyte/macrophage-producing MMP-7 protein. The high MMP-7 expression in nodules was associated with the single-nucleotide polymorphism (SNP) rs11568818 (-181A>G, MMP-7 promoter) and more active inflammation within the nodule lesions. Patients with such nodules had significantly earlier age of RA onset. Our findings indicate that the expression of MMP-1 and MMP-3 occurs relatively independent of the tissue microenvironment with substantial expression also at extra-articular sites. MMP-12 expression reflects the involvement of monocyte/macrophages in rheumatoid inflammation. Evidence for the association between the rs11568818 SNP and increased MMP-7 expression is restricted to nodules, which indicates that consequences of the MMP-7 polymorphism are likely to manifest within aspects of immune/inflammatory activity that are monocyte/macrophage-mediated.
Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
M G
MG
Kazantseva
N A
NA
Hung
J
J
Highton
P A
PA
Hessian
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012218:Rheumatoid Nodule / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D053508:Matrix Metalloproteinase 12; D020781:Matrix Metalloproteinase 1