Regulation of TNFalpha and interleukin-10 production by prostaglandins I(2) and E(2): studies with prostaglandin receptor-deficient mice and prostaglandin E-receptor subtype-selective synthetic agonists
| Autor: | Yukihiko Sugimoto, Hiroaki Naraba, Fumitaka Ushikubi, Shuichi Ohuchida, Iku Utsunomiya, Akinori Ueno, Shuh Narumiya, Takayuki Maruyama, Atsushi Ichikawa, Shiho Shinomiya, Koichi Yuki, Sachiko Oh-ishi |
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| Rok vydání: | 2001 |
| Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class Prostaglandin E2 receptor medicine.medical_treatment Receptors Prostaglandin Prostaglandin Biology Biochemistry Dinoprostone chemistry.chemical_compound Mice Internal medicine medicine Cyclic AMP Animals Receptors Prostaglandin E RNA Messenger Prostaglandin E2 Prostaglandin receptor Pharmacology Tumor Necrosis Factor-alpha Zymosan Epoprostenol Interleukin-10 Mice Inbred C57BL Interleukin 10 Cytokine Endocrinology chemistry Macrophages Peritoneal lipids (amino acids peptides and proteins) Female medicine.drug Prostaglandin E |
| Zdroj: | Biochemical pharmacology. 61(9) |
| ISSN: | 0006-2952 |
| Popis: | To know which receptors of prostaglandins are involved in the regulation of TNFalpha and interleukin 10 (IL-10) production, we examined the production of these cytokines in murine peritoneal macrophages stimulated with zymosan. The presence of PGE(2) or the PGI(2) analog carbacyclin in the medium reduced the TNFalpha production to one-half, whereas IL-10 production increased several fold; and indomethacin caused the reverse effects, suggesting that endogenous prostaglandins may have a regulatory effect on the cytokine production. Among prostaglandin E (EP) receptor-selective synthetic agonists, EP2 and EP4 agonists caused down-regulation of the zymosan-induced TNFalpha production, but up-regulation on the IL-10 production; while EP1 and EP3 agonists showed no effect. Macrophages harvested from prostaglandin I (IP) receptor-deficient mice showed the up- and down-regulatory effects on the cytokine production by the EP2 and EP4 agonists or PGE(2), but no effect was obtained by carbacyclin. On the contrary, macrophages from EP2-deficient mice showed the effect by PGE(2), carbacyclin, and the EP4 agonist, but not by the EP2 agonist; and the cells from EP4-deficient mice showed the effect by PGE(2), carbacyclin, and EP2 agonist, but not by the EP4 agonist. These functional effects of prostaglandins well accorded with the mRNA expression of TNFalpha and IL-10 when such expression was examined by the RT-PCR method. The peritoneal macrophages from normal mice expressed IP, EP2, and EP4 receptors, but not EP1 and EP3, when examined by RT-PCR. Thus the results suggest that PGI(2) and PGE(2) generated simultaneously with cytokines by macrophages treated with zymosan may influence the cytokine production through IP, EP2, and EP4 receptors. |
| Databáze: | OpenAIRE |
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