Characterization of collagenase 3 (matrix metalloproteinase 13) messenger RNA expression in the synovial membrane and synovial fibroblasts of patients with rheumatoid arthritis
| Autor: | Claudia Schulze Westhoff, Dirk Freudiger, Peter Petrow, Christine Seyfert, Josef Zacher, J�rg Kriegsmann, Thomas Pap, Steffen Gay, Peter Stiehl, Erika Gromnica-Ihle, Dirk Wernicke |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Phosphodiesterase Inhibitors Immunology In situ hybridization Biology Arthritis Rheumatoid Rheumatology 1-Methyl-3-isobutylxanthine Matrix Metalloproteinase 13 Cyclic AMP medicine Humans Immunology and Allergy Pharmacology (medical) Collagenases RNA Messenger Northern blot Fibroblast Cells Cultured In Situ Hybridization Aged Aged 80 and over Messenger RNA Colforsin Synovial Membrane Fibroblasts Middle Aged Molecular biology Enzyme Activation Radiography medicine.anatomical_structure Bucladesine Gene Expression Regulation Cell culture Collagenase Interstitial collagenase Female Synovial membrane Adenylyl Cyclases medicine.drug |
| Zdroj: | Arthritis & Rheumatism. 42:1517-1527 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/1529-0131(199907)42:7<1517::aid-anr27>3.0.co;2-g |
| Popis: | Objective To study the localization and cell type–specific expression of collagenase 3 messenger RNA (mRNA) in the synovial membrane, its regulation in primary synovial fibroblasts, and the correlation with systemic markers of inflammation and radiographic damage in rheumatoid arthritis (RA). Methods The expression of collagenase 3 mRNA was characterized by Northern blot analysis, reverse transcriptase–polymerase chain reaction, and in situ hybridization. Immunohistochemical detection of cell type–specific antigens was used in combination with in situ hybridization of collagenase 3 mRNA to characterize the cellular origin of collagenase 3 mRNA expression. Results Collagenase 3 mRNA was detected in synovial membrane specimens of 21 of 36 RA patients (58%) and correlated with an increase in erythrocyte sedimentation rate (P < 0.05) and C-reactive protein levels (P < 0.005). Collagenase 3 mRNA was localized in fibroblast-like cells of the lining and sublining layers, and at the synovial membrane–cartilage interface. Four of 10 primary synovial fibroblast cell cultures showed basal expression of collagenase 3 mRNA, which was stimulated 2–4-fold upon interleukin-1β or tumor necrosis factor α treatment and, in contrast to interstitial collagenase mRNA, 5–10-fold by increasing the intracellular level of cAMP. The stimulation by cAMP analogs was completely abolished by protein kinase A inhibitors. Conclusion Some RA patients show collagenase 3 mRNA expression in the synovial membrane, which correlates with elevated levels of systemic markers of inflammation in these patients. In synovial fibroblasts, the expression of collagenase 3 and interstitial collagenase mRNA is differentially regulated by distinct protein kinase signal transduction pathways. |
| Databáze: | OpenAIRE |
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