Interleukin-1 up-regulates transcription of its own receptor in a human fibroblast cell line TIG-1: role of endogenous PGE2 and cAMP.
The regulation of interleukin-1 receptor (IL-1R) mRNA expression by IL-1 in a human lung fibroblast cell line (TIG-1) was investigated. After 2 h of stimulation with human recombinant IL-1 alpha or IL-1 beta, the levels of T cell/fibroblast-type IL-1R mRNA increased, and the elevation was sustained for at least 72 h. IL-1 also stimulated synthesis of prostaglandin E2 (PGE2) and secondary cAMP accumulation. Exogenously added PGE2 increased the levels of both IL-1R mRNA and intracellular cAMP. Forskolin, cholera toxin and 8-Bromo adenosine (8-Br-cAMP) all increased IL-1R mRNA levels. Indomethacin blocked IL-1 stimulation of IL-1R mRNA expression, PGE2 production and cAMP. 125I-labeled IL-1 alpha-binding studies showed that this cell line expresses 2.6 x 10(4) IL-1R per cell with a Kd of 5.1 x 10(-10) M. After treatment of the cells with IL-1, the level of IL-1R increased over that of control cells. PGE2 also increased IL-1R without alteration in its affinity. Cross-linking experiments indicate that this cell line expresses the 80-kDa receptor molecule before and after treatment with PGE2; the molecular mass corresponds to the T cell/fibroblast type I IL-1R. These results indicate that IL-1 does not directly stimulate expression of IL-1R mRNA or cell surface IL-1R, but only indirectly by stimulation of endogenous PGE2.
Takii
T
T
Division of Cell Biology, Fujita-Gakuen Health University, Aichi, Japan.
Akahoshi
T
T
Kato
K
K
Hayashi
H
H
Marunouchi
T
T
Onozaki
K
K
D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000235:genetics*; D017472:Receptors, Interleukin-1; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation
D007375:Interleukin-1; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D015232:Dinoprostone