Interleukin 4 (IL) 4 up-regulates gene and surface IL 1 receptor type I in murine T helper type 2 cells.
The T cell-derived cytokine interleukin (IL) 4 is known to increase the proliferative response of T cells stimulated with IL 1. IL 4 is also an autocrine growth factor for type II T helper cells (Th2) cells. In the present studies, we examined the effect of murine recombinant IL 4 on the expression of the IL 1 receptor type I (IL 1RtI) in murine Th2 cell lines at the mRNA and surface level. Using a specific anti-murine IL 1RtI monoclonal antibody and flow microfluorometry, we found that IL 4 increased the surface expression of IL 1RtI in a dose-dependent manner. In D10S cells, a subline of the Th2 cell line D10.G4.1, 50-500 pg/ml IL 4 up-regulated the receptor 1.8- to 3.2-fold (p less than 0.05). This up-regulation was also seen at the mRNA level. The effect was not due to increased stability of the mRNA, since IL 4 did not modify the half-life of IL 1RtI mRNA. IL 4 also up-regulated IL 1RtI on CDC25 cells, another Th2 cell line. However, we did not observe an effect of IL 4 on gene expression of IL 1RtI in BALB/c 3T3 fibroblasts. IL 2 and IL 4 showed an additive effect in up-regulating IL 1RtI and D10S cells. These studies indicate that IL 4 up-regulates IL 1RtI in murine Th2 cells by increasing gene expression for IL 1RtI without affecting mRNA stability. Thus, IL 4 production by Th2 cells may amplify the immune response via up-regulation of IL 1RtI.
Koch
K C
KC
Department of Medicine, Tufts University School of Medicine, Boston, MA.
Ye
K
K
Clark
B D
BD
Dinarello
C A
CA
D000818:Animals; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics; D017472:Receptors, Interleukin-1; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015854:Up-Regulation
D007375:Interleukin-1; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D015847:Interleukin-4