Induction of intracellular interleukin-1 beta signals via type II interleukin-1 receptor in human gingival fibroblasts.
The type II interleukin-1 receptor (IL-1RII) has been thought to be incapable of transducing signals to cells because of its short intracellular domain, while type I IL-1 receptor (IL-1RI) does transduce signals. Since over-expression of IL-1RII has been demonstrated to inhibit cytokine production in the fibroblastic cell line, it has been proposed to use IL-1RII to prevent IL-1-induced inflammation in connective tissue. In this study, trace amounts of IL-1RII mRNA expression were detected in human gingival fibroblasts (HGFs), which are affected by cytokines in inflammatory periodontal disease. Cloning of the cDNA encoding IL-1RII expressed in HGFs revealed 3 amino acid substitutions in the extracellular domain, when compared with the 408 residues predicted from human B-cells. Over-expression of IL-1RII on HGFs by gene transfer down-regulated the expression of IL-1 beta mRNA and IL-6 mRNA in response to IL-1 beta stimulation, while the expression of IL-8 mRNA was not affected. In the IL-1RII-transfected HGFs, phosphorylation of 25- and 74-kDa proteins was up-regulated upon IL-1 beta stimulation in the transfected HGFs. The phosphorylation of these proteins was suppressed by the addition of a neutralizing antibody against IL-1RII. These results suggest that the IL-1RII may regulate HGFs expression of cytokine mRNA upon IL-1 beta stimulation, possibly by altering the IL-1RI-dependent signals.
Chou
H H
HH
Department of Periodontology and Endodontology, Okayama University Dental School, Japan.
Takashiba
S
S
Maeda
H
H
Naruishi
K
K
Nishimura
F
F
Arai
H
H
Lu
H
H
Murayama
Y
Y
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1