Synovial fibroblasts from rheumatoid arthritis patients differ in their regulation of IL-16 gene activity in comparison to osteoarthritis fibroblasts
| Autor: | Wilhelm K. Aicher, Michaela Weis-Klemm, Thomas Pap, Dorothee Reyer, Dorothea Alexander, Heike Schützle, Juliane K. Franz |
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| Rok vydání: | 2004 |
| Předmět: |
Cell Extracts
Physiology medicine.medical_treatment Arthritis Protein Serine-Threonine Kinases Arthritis Rheumatoid chemistry.chemical_compound Osteoarthritis medicine Cyclic AMP Staurosporine Humans RNA Messenger Protein kinase C Cells Cultured Interleukin-16 Forskolin business.industry Colforsin Synovial Membrane Fibroblasts medicine.disease Molecular biology Blot Cytokine medicine.anatomical_structure chemistry Gene Expression Regulation Immunology Synovial membrane Signal transduction business medicine.drug Interleukin-1 Signal Transduction |
| Zdroj: | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 14(4-6) |
| ISSN: | 1015-8987 |
| Popis: | Background: In rheumatoid arthritis (RA), synovial fibroblast-like cells (SF) contribute significantly to articular inflammation. They express distinct patterns of genes associated with cell proliferation and differentiation and elevated levels of cytokines and chemoattractant factors, including IL-16. Here we investigated pathways regulating IL-16 expression in fibroblasts from RA patients in comparison to fibroblasts from osteoarthritis (OA) patients. Methods: Fibroblasts were isolated from dermal and articular biopsies, expanded and pathways of IL-16 induction were investigated by real time quantitative RT/PCR, immuno blot and ELISA. Results: Stimulation of cAMP dependent signal transduction by forskolin induced prominent IL-16 RT/PCR signals in OA-DF and OA-SF. In contrast, in RA-DF and RA-SF staurosporine significantly augmented IL-16 RT/PCR signals, but forskolin induced less IL-16 transcript amounts. Activation of protein kinase C by PMA induced a significant IL-16 response only in RA-SF. Addition of IL-1β or TNF-α did not upregulate IL-16 mRNA but secretion of the mature IL-16 cytokine was activated in serum starved cells in presence of IL-1β. Conclusion: Our results suggest that RA fibroblasts differ from OA fibroblasts with respect to their sensitivities to kinase/phospatase signal transduction pathways. The enhanced expression of IL-16 in the synovial membrane early in RA vs OA may be associated in part with these distinct signaling responses. |
| Databáze: | OpenAIRE |
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