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
Takii, T.; Hayashi, H.; Marunouchi, T.; Onozaki, K.
Lymphokine and Cytokine Research 13(3): 213-219
1994
ISSN/ISBN: 1056-5477 PMID: 7948430 Document Number: 437754
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 E-2 (PGE-2) synthesis and subsequent intracellular cAMP accumulation in a human lung fibroblast cell line (TIG-1). In this study, the effect IL-1 on IL-1R mRNA expression was investigated in the absence of PGE-2 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.