ABSTRACT
Immunohistochemical staining of formalin fixed, paraffin embedded tissue sections of OSF for MMPs-1,2,9 and their tissue inhibitors TIMP-1and 2 was performed using monospecific antibodies coupled with gelatin zymography (MMP-2 and 9) for measuring enzymatic activity quantitatively and for distinguishing the active from the inactive variants of enzymes. The present study, contrary to earlier reports, recorded statistically significant increase in the levels of stromal expression of MMP-1, MMP-2 and MMP-9 and TIMP-1 and TIMP-2 using monospecific antibodies reacting against tissue antigens.The simultaneous increase in reactivity of MMPs and TIMPs poise difficulty in interpretingthe results of this study. The possible reasons for this result, against the backdrop of existing knowledge, were attempted in this study.
Subject(s)
Adult , Antibodies, Monoclonal/diagnosis , Biopsy , Case-Control Studies , Epithelial Cells/enzymology , Female , Humans , Immunohistochemistry , Male , Matrix Metalloproteinase 1/analysis , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 9/analysis , Mouth Mucosa/enzymology , Oral Submucous Fibrosis/enzymology , Prospective Studies , Stromal Cells/enzymology , Tissue Inhibitor of Metalloproteinase-1/analysis , Tissue Inhibitor of Metalloproteinase-2/analysisABSTRACT
The aim of this study was to investigate the expression and localization of cyclooxygenase-1 and -2 (COX-1 and COX-2) in synovial tissues from patients with rheumatoid arthritis (RA). Synovial tissues from 9 patients with RA and 5 patients with osteoarthritis (OA) were examined for COX-1 and COX-2 expressions by immunohistochemical staining using 2 polydonal COX-1 and COX-2 antibodies. In RA synovia, synovial lining cells showed intense immunostaining for COX-1, whereas slight to moderate staining was observed in inflammatory cells, stromal fibroblast-like cells and vascular endothelial cells. There was no significant difference in COX-1 expression between RA and OA synovia. The localization of COX-2 expression dearly differed from that of COX-1 expression, being most intense in inflammatory cells. However, there was no difference in COX-1 and COX-2 expressions between RA and OA synovial tissues. Our observations support that inflammatory mechanisms modulated by COX-1 and COX-2 in chronic RA synovium might be similar to those in chronic OA synovium.
Subject(s)
Adult , Aged , Female , Humans , Male , Arthritis, Rheumatoid/pathology , Arthritis, Rheumatoid/enzymology , Cell Division , Fibrin/metabolism , Isoenzymes/metabolism , Isoenzymes/biosynthesis , Middle Aged , Neutrophil Infiltration , Osteoarthritis/enzymology , Prostaglandin-Endoperoxide Synthases/metabolism , Prostaglandin-Endoperoxide Synthases/biosynthesis , Stromal Cells/pathology , Stromal Cells/enzymology , Synovial Membrane/pathology , Synovial Membrane/enzymologyABSTRACT
Increased production of matrix metalloproteinases (MMPs) has been associated with increases in invasive and metastatic potential in many types of human carcinoma. Tissue inhibitors of metalloproteinase (TIMP)-1 inhibits most interstitial collagenases and MMP-9. TIMP-2 binds specifically and noncovalently to the pro-form of MMP-2 and inhibits its enzyme activity. In this study, we examined TIMP-1 and TIMP-2 expressions in relation to clinicopathological variables in colorectal carcinoma with in situ hybridization and immunohistochemistry. TIMP-1 and TIMP-2 expressions were localized overwhelmingly to pericancer stromal cells, while malignant and normal mucosal cells were weak or negative. Strong stromal TIMP-1 immunoreactivity correlated with Dukes' stage (p=0.022), status of lymph node metastasis (p=0.044) and poor survival (p= 0.005). The degree of immunohistochemical staining of TIMP-2 did not correlate with all clinicopathological variables. The correlation between enhanced TIMP-1 expression and advanced stage and poor survival suggest a growth promoting activity of TIMP-1 in colorectal carcinoma.