Interleukin-4 inhibits cyclo-oxygenase-2 expression and prostaglandin E2 production by human mature dendritic cells
Article first published online: 16 JAN 2007
Volume 120, Issue 1, pages 83–89, January 2007
How to Cite
Teloni, R., Giannoni, F., Rossi, P., Nisini, R. and Gagliardi, M. C. (2007), Interleukin-4 inhibits cyclo-oxygenase-2 expression and prostaglandin E2 production by human mature dendritic cells. Immunology, 120: 83–89. doi: 10.1111/j.1365-2567.2006.02482.x
- Issue published online: 16 JAN 2007
- Article first published online: 16 JAN 2007
- Received 10 May 2006; revised 29 August 2006; accepted 29 August 2006.
- dendritic cells;
- prostaglandin E2
Interleukin-4 (IL-4) is considered the key cytokine for inducing T helper type 2 (Th2) cell differentiation, while interferon-γ and IL-12 are pivotal cytokines for Th1 immune responses. Paradoxically, IL-4 has also been demonstrated to enhance IL-12 production by dendritic cells, suggesting an IL-4-dependent regulatory feedback of the Th1/Th2 system. In addition, prostaglandin E2 (PGE2), a lipid mediator of inflammation, has been implicated in the enhancement of Th2-type responses acting directly on T and B lymphocytes. PGE2 synthesis is dependent on the serial engagement of various enzymes, among which the inducible cyclo-oxygenase-2 (COX-2) exerts a critical role in monocytes and dendritic cells. In this study we demonstrate that IL-4 inhibits COX-2 gene expression and consequently prevents secretion of PGE2 by mature human dendritic cells. We also show that PGE2 does not regulate IL-12 and IL-10 production by dendritic cells in an autocrine fashion. Hence, we suggest that IL-4 may exploit an IL-12-independent regulatory feedback of the Th1/Th2 system through PGE2 inhibition.