Interleukin 1 stimulates its own receptor expression on human fibroblasts through the endogenous production of prostaglandin(s).

The regulation of interleukin 1 receptor (IL 1R) expression on human dermal fibroblasts was investigated. On exposure to IL 1 for 3 h at 37 degrees C, the capacity of fibroblasts to bind 125I-labeled human recombinant IL 1 alpha (125I-IL 1 alpha) was reduced by 75%. The IL 1 binding capability of the fibroblasts was restored to control levels by 16 h after removal of unbound IL 1, and then increased to about twofold over that of control cells by 48 h. This later enhancement of IL 1 receptor expression after IL 1 treatment was abolished by indomethacin. Addition of exogenous (PGE1 and PGE2, also analogues of AMP, or forskolin increased the specific binding of 125I-IL 1 alpha to fibroblasts. Scatchard analysis indicated that PGE2 increased the number of IL 1R from approximately 1.6 X 10(3) to 5.4 X 10(3) per cell without change in the binding affinity. These data suggest that the later IL 1-induced up-regulation of IL 1R is mediated by IL 1 stimulation of endogenous prostaglandin production. The combination of PGE2 and prednisolone increased the number of IL 1R on fibroblasts in an additive manner.