Expression of the familial Mediterranean fever gene and activity of the C5a inhibitor in human primary fibroblast cultures
| Autor: | Polina Stepensky, Sima Calco, Eli Shapiro, Shlomit Eisenberg, Suzan Abedat, Ariela Bar-Gil-Shitrit, Simcha Urieli-Shoval, Yaacov Matzner, Yehudit Azar |
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| Rok vydání: | 2000 |
| Předmět: |
Immunology
Familial Mediterranean fever Gene Expression Complement C5a Biology Pyrin domain Biochemistry Gene expression medicine Humans Interleukin 8 Fibroblast Cells Cultured Complement Inactivator Proteins Reverse Transcriptase Polymerase Chain Reaction Interleukin-8 Synovial Membrane Interleukin Proteins Cell Biology Hematology Fibroblasts Pyrin MEFV medicine.disease Molecular biology Familial Mediterranean Fever Cytoskeletal Proteins medicine.anatomical_structure Cell culture Tetradecanoylphorbol Acetate Peritoneum Interleukin-1 |
| Zdroj: | Blood. 96:727-731 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Familial Mediterranean fever (FMF) is an inherited disease whose manifestations are acute but reversible attacks of sterile inflammation affecting synovial and serosal spaces. The FMF gene (MEFV) was recently cloned, and it codes for a protein (pyrin/marenostrin) homologous to known nuclear factors. We previously reported the deficient activity of a C5a/interleukin (IL)–8 inhibitor, a physiologic regulator of inflammatory processes, in FMF serosal and synovial fluids. We now describe the concomitant expression ofMEFV and C5a/IL-8–inhibitor activity in primary cultures of human fibroblasts. Fibroblasts grown from synovial and peritoneal tissues displayed C5a/IL-8–inhibitor activity that could be further induced with phorbol myristate acetate (PMA) and IL-1β. Very low levels of chemotactic inhibitor were evident in skin fibroblast cultures or in peritoneal and skin fibroblasts obtained from FMF patients. MEFV was expressed in peritoneal and skin fibroblasts at a lower level than in neutrophils and could be further induced by PMA and IL-1β. In the FMF cultures, the MEFV transcript carried the M694V mutation, consistent with the genetic defect found in patients with this disease. MEFV was also expressed in other cell lines that do not produce C5a/IL-8 inhibitor. These findings suggest that human primary fibroblast cultures express MEFV and produce C5a/IL-8–inhibitor activity. The interrelationship between pyrin, the MEFV product, and the C5a/IL-8 inhibitor requires further investigation. |
| Databáze: | OpenAIRE |
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