| Title: |
Cyclic nucleotide phosphodiesterase type IV participates in the regulation of IL-10 and in the subsequent inhibition of TNF-α and IL-6 release by endotoxin-stimulated macrophages |
| Authors: |
Kambayashi, T; Jacob, C O; Zhou, D; Mazurek, N; Fong, M; Strassmann, G |
| Source: |
The Journal of Immunology ; volume 155, issue 10, page 4909-4916 ; ISSN 1550-6606 0022-1767 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
1995 |
| Description: |
We have recently shown that PGE2 inhibits the release of TNF-α from LPS-stimulated murine peritoneal macrophages via a feedback mechanism involving IL-10. Here we demonstrate that a rolipram-sensitive phosphodiesterase (PDE) type IV participates in the regulation of IL-10 synthesis. Selective PDE IV inhibitors (rolipram and RO-20-1724), but not selective inhibitors of other types of PDE, significantly augment marcrophage IL-10 production and contribute to the inhibition of TNF-α and IL-6 release. The addition of rolipram to LPS-stimulated macrophages results in the accumulation of cAMP and in the significant augmentation of IL-10 release. Competitive PCR analysis reveals that the drug dramatically increases IL-10 mRNA, but does not affect TNF-α mRNA. The inhibitory effect of rolipram on TNF-α can be significantly but incompletely reversed by anti-IL-10 Ab, whereas the effect of the drug on IL-6 can be completely reversed by anti-IL-10. In endotoxemic mice, the administration of rolipram increases serum IL-10 and reduces TNF-α and IL-6 levels. Northern blot analysis of spleens from these mice shows that rolipram increases IL-10 mRNA, whereas TNF-α mRNA remains largely unchanged. These results suggest that a rolipram-sensitive PDE type IV is involved in the production of IL-10 and in turn contributes to the inhibition of TNF-α and IL-6 release. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.155.10.4909 |
| Availability: |
https://doi.org/10.4049/jimmunol.155.10.4909; https://academic.oup.com/jimmunol/article-pdf/155/10/4909/62365008/7594495.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.2C1A5FC8 |
| Database: |
BASE |