Human fibroblasts express functional IL-2 receptors formed by the IL-2R alpha- and beta-chain subunits: association of IL-2 binding with secretion of the monocyte chemoattractant protein-1.

Abstract

Expression of IL-2R was examined on human fibroblasts isolated from different tissues. By specific binding assay it is shown that [125I]IL-2 bound to subconfluent adult bone marrow and embryonic skin and lung fibroblasts. The presence of binding sites for IL-2 was also confirmed by immunofluorescence and flow cytometry analysis using mAbs specific for the p55 IL-2R alpha (anti-CD25), p75 IL-2R beta, and p64 IL-2R gamma subunits. Fibroblasts also constitutively transcribed the genes coding for IL-2R alpha and IL-2R beta and accumulated their respective mRNAs but failed to exhibit the IL-2R gamma-chain on the mRNA and protein level. Although addition of IL-2 to fibroblast cultures did not significantly alter growth kinetics of these cells, the IL-2R complex displayed by fibroblasts appeared to be functional in that addition of IL-2 to these cells led to enhanced expression of the JE gene coding for the monocyte chemoattractant protein-1 (MCP-1). Enhancement of fibroblast MCP-1/JE gene expression by IL-2 appeared to result from delayed MCP-1/JE mRNA decay rather than as a consequence of an acceleration of the MCP-1/JE gene transcription rate. IL-2 had, however, no effect on the expression of other cytokine genes including IL-1, IL-5, IL-6, IL-7, IL-8, IL-9, granulocyte-macrophage-CSF, macrophage-CSF or TNF. These observations suggest that the range of cellular targets of IL-2 is broader than originally appreciated. IL-2 may thus serve to integrate fibroblasts and monocytes into a coordinated response of the connective tissue initiated by T lymphocytes.