Opposite effects of interferon-γ and prostaglandin E2 on tumor necrosis factor and interleukin-10 production in microglia: A regulatory loop controlling microglia pro- and anti-inflammatory activities
✍ Scribed by Francesca Aloisi; Roberta De Simone; Sandra Columba-Cabezas; Giulio Levi
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 201 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Following brain injury, microglial cells produce proand anti-inflammatory cytokines
, such as tumor necrosis factor (TNF) and interleukin-10 (IL-10). IL-10 provides an efficient autocrine mechanism for controlling microglia activation. To elucidate the mechanisms that regulate the cytokine profile of microglia, we examined the effects of several immunomodulators on IL-10 and TNF production by cultured mouse microglia. Lipopolysaccharide (LPS) was the only inducer of IL-10 and TNF gene expression and secretion. The T helper 1-type cytokine interferon-␥ (IFN-␥) induced TNF transcripts, but not TNF secretion, and suppressed LPS-induced IL-10 mRNA and secretion by microglia. Opposite to IFN-␥, the lipid mediator prostaglandin E 2 (PGE 2 ) enhanced the LPS-induced production of IL-10 and inhibited that of TNF. The effects of PGE 2 on cytokine gene expression and secretion were antagonized by IFN-␥. Agents that increase cAMP levels mimicked the action of PGE 2 on cytokine secretion, indicating the involvement of cAMP-coupled prostaglandin receptors. In conclusion, IFN-␥ and PGE 2 , two mediators released at inflammatory sites, differentially regulate the production of a proinflammatory and an anti-inflammatory cytokine in microglia. We suggest that the activity and role of microglia in the damaged CNS could be finely tuned by the local concentration ratio of these mediators.