Interleukin-1 down-regulates type I interleukin 1 receptor mRNA expression in a human fibroblast cell line TIG-1 in the absence of prostaglandin E2 synthesis.
We have shown that interleukin-1 (IL-1) up-regulates transcription of its own receptor and number of cell surface IL-1 receptor (IL-1R) type I molecule through induction of prostaglandin E2 (PGE2) synthesis and subsequent intracellular cAMP accumulation in a human lung fibroblast cell line (TIG-1). In this study, the effect of IL-1 on IL-1R mRNA expression was investigated in the absence of PGE2 synthesis. In the presence of indomethacin, an inhibitor of cyclooxygenase, IL-1 inhibited the expression of IL-1R mRNA within 4 h after treatment, and the inhibition sustained at least for 24 h. IL-1 beta as well as IL-1 alpha at higher than 1 U/ml exhibited the inhibitory effect. The inhibitory effect of IL-1 was inhibited by cycloheximide suggesting that de novo protein synthesis is required. IL-1 appeared to destabilize IL-1R mRNA within 30 min after treatment of the cells. Furthermore, this effect of IL-1 was not observed in a synthetic medium and was dependent on serum concentrations indicating that a serum component(s) is involved. These results indicate that IL-1 regulates IL-1R mRNA expression in both a positive and negative manner, and that the negative effect represents a negative feedback mechanism.
Takii
T
T
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Hayashi
H
H
Marunouchi
T
T
Onozaki
K
K
D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects*; D005246:Feedback; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin