Differential regulation of tumour necrosis factor receptors (TNF-R) by IL-4; upregulation of P55 and P75 TNF-R on synovial joint mononuclear cells
| Autor: | David Wallach, Deena L. Gibbons, Brian M. J. Foxwell, Fionula M. Brennan, Andrew P. Cope, Dan Aderka, Marc Feldmann, Ravinder N. Maini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
musculoskeletal diseases
Knee Joint T cell Immunology Down-Regulation Biochemistry Peripheral blood mononuclear cell Monocytes Receptors Tumor Necrosis Factor Flow cytometry Cell Line HeLa Arthritis Rheumatoid Osteoarthritis Synovial Fluid medicine Tumor Cells Cultured Immunology and Allergy Humans Receptor Molecular Biology Interleukin 4 Cells Cultured biology medicine.diagnostic_test business.industry Tumor Necrosis Factor-alpha Arthritis hemic and immune systems Hematology biology.organism_classification Molecular biology Burkitt Lymphoma biological factors Recombinant Proteins Up-Regulation medicine.anatomical_structure Cell culture Tumor necrosis factor alpha Interleukin-4 business HeLa Cells |
| Popis: | Interleukin 4 (IL-4) has previously been shown to downregulate the production of proinflammatory cytokines such as TNF-alpha, and hence has been considered to be a potential anti-inflammatory agent. In this study we have investigated the effects of IL-4 on the expression of both p55 and p75 TNF receptors (TNF-R) by flow cytometry and radioligand binding analyses and demonstrate that IL-4 downregulates both p55 and p75 TNF-R on HeLa and Jijoye cell lines in a dose dependent manner. IL-4 reduced the number of p55 TNF-R on HeLa cells from 6400 (Kd 5.1 nM) to 3900 (Kd 3.7 nM), and p75 TNF-R on Jijoye cells from 4800 (Kd 1.6 nM) to 3250 (Kd 1.5 nM). However, different effects were observed on peripheral blood mononuclear cells (PBMC). IL-4 inhibited the increase in p55 and p75 TNF-R on PBMC following adherence, whereas IL-4 upregulated p75 TNF-R expressed on PHA induced T cell blasts. To assess further the possible anti-inflammatory properties of IL-4, we studied its effects on synovial joint mononuclear cell cultures from 15 patients with inflammatory synovitis. In contrast to the differential effects of IL-4 on monocytes and T cells, IL-4 upregulated both p55 (P < 0.05) and p75 TNF-R (P < 0.005) on synovial joint cells in culture. IL-4 treatment caused a small decrease in levels of bioactive TNF-alpha in RA synovial culture supernatants, together with an increase in soluble p75 TNF-R levels although differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|