Increased acinar damage of salivary glands of patients with Sjögren's syndrome is paralleled by simultaneous imbalance of matrix metalloproteinase 3/tissue inhibitor of metalloproteinases 1 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 ratios.
OBJECTIVE
Previous findings in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS) suggest that increased activity and expression of matrix metalloproteinase 9 (MMP-9) and MMP-3 trigger the destruction of acinar structures in these glands. Tissue inhibitors of matrix metalloproteinases (TIMPs) tightly control MMP activity, and TIMP expression is an important modulator of effects attributed to MMPs. This study was undertaken to investigate the correlation between the balance of MMPs/TIMPs in the LSGs of SS patients and the degree of inflammatory infiltration and acinar structure integrity.


METHODS
Three groups of SS patients classified according to focus score and residual tissue were studied. The expression of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 was examined at the messenger RNA and protein levels. The ratio of MMP/TIMP expression (R value) was calculated. Focus score and acinar structure were evaluated by histologic analysis.


RESULTS
In SS patients the MMP-3/TIMP-1 ratio was higher than 1 and the MMP-9/TIMP-1 ratio was much higher than 1 whereas the MMP-2/TIMP-2 ratio nearly equaled 1, suggesting elevated proteolytic activity due mainly to MMP-9. R values were independent of the focus score of inflammatory cells, but correlated well with the dramatic changes observed in morphologic integrity of acini, as revealed mainly by the lack of nuclear polarity. Acinar changes were more evident when R values for both MMP-9/TIMP-1 and MMP-3/TIMP-1 were higher.


CONCLUSIONS
This study provides evidence that an altered balance between MMPs and their inhibitors is associated with acinar damage. Since salivary gland acinar cells express both MMPs and TIMPs, these cells may play an important role in extracellular matrix destruction and in the LSG pathophysiology in SS.
Pérez
Paola
P
University of Chile, Santiago, Chile.
Kwon
Yoon-Jeoung
YJ
Alliende
Cecilia
C
Leyton
Lisette
L
Aguilera
Sergio
S
Molina
Claudio
C
Labra
Cecilia
C
Julio
Marcela
M
Leyton
Cecilia
C
González
María-Julieta
MJ
D015153:Blotting, Western; D006801:Humans; D007124:Immunoenzyme Techniques; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012470:Salivary Glands, Minor / Q000201:enzymology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000201:enzymology* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9