Abstract

We examined the roles of prostaglandin receptors regulating tumor necrosis factor-alpha (TNFα) and IL-10 production by zymosan-stimulated murine peritoneal macrophages. During the stimulation with zymosan for 5 h, the presence of PGE 2 or carbacyclin suppressed the TNFα production, whereas it increased that of IL-10; and indomethacin caused the reverse effects, suggesting that endogenous prostaglandins may have regulatory effects on the cytokine production. Among the EP subtype-selective synthetic agonists used, EP2 and EP4 agonists caused down-regulation of the TNFα production, but up-regulation of the IL-10 production; whereas EP1 and EP3 agonists showed no effect. Macrophages harvested from IP, EP2 or EP4 receptor-deficient mice lacked the up- and down-regulatory effects on the cytokine production by each corresponding agonist. These effects of prostaglandins agreed well with the mRNA expression of TNFα and IL-10 when mRNA levels were examined by the RT-PCR method. Thus, the results suggest that endogenous PGI 2 and PGE 2 may exert their anti-inflammatory influence on the cytokine production through IP, EP2, and EP4 receptors.

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