Prostaglandin E2-dependent IL-23 production in aged murine dendritic cells
| Autor: | Kevin P. High, Rabab El Mezayen, Rebecca G. Myer |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Aging medicine.medical_specialty Cell Survival medicine.medical_treatment Bone Marrow Cells Biology Biochemistry Interleukin-23 Dinoprostone Article Mice Endocrinology Immune system Transforming Growth Factor beta Internal medicine Genetics medicine Animals Receptors Prostaglandin E Prostaglandin E2 Receptor Molecular Biology Cellular Senescence Interleukin-6 Cell Biology Transforming growth factor beta Dendritic Cells Cell biology Up-Regulation Mice Inbred C57BL Toll-Like Receptor 4 Cytokine Toll-Like Receptor 7 Toll-Like Receptor 8 TLR4 biology.protein Cytokines Th17 Cells Signal transduction Cell aging medicine.drug Signal Transduction |
| Zdroj: | Experimental gerontology. 45(11) |
| ISSN: | 1873-6815 |
| Popis: | CD4+ T cells of the Th17 subtype are over-represented in the aged immune system. Dendritic cells (DC) play a critical role in naive CD4+ T cell differentiation. However, expression of cytokines by aged DC that promote differentiation or survival of Th17 cells has not been extensively investigated. Using bone marrow-derived DC from C57BL/6 mice of different ages we compared cytokine production after DC activation by Toll-like receptor agonists for TLR4 and/or TLR7/8. DC-derived TNF-α and IL-12p70 production and expression of DC co-stimulatory molecules did not vary significantly by age indicating that TLR expression, function and signal transduction were intact in aged DC. There were relatively minor age-related changes in TGF-β and IL-6 which promote Th17 differentiation, but IL-23, a Th17-suvival cytokine, increased more than 40-fold across the lifespan. DC-derived prostaglandin E2 (PGE2) also increased with age and the up-regulation of IL-23 expression by aged DC was blocked by indomethacin that prevents PGE2 production, and by antagonists of PGE2 receptors. Exogenous PGE2 added to DC cultures further enhanced IL-23 production from aged but not young DCs. These data indicate that age-related changes in DC PGE2 production are necessary, but not sufficient to induce DC IL-23 production. Such changes may play a role in the expansion of Th17 cells in the aged immune system. |
| Databáze: | OpenAIRE |
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