Cultured human fibroblasts express constitutive IL-16 mRNA: Cytokine induction of active IL-16 protein synthesis through a caspase-3-dependent mechanism

Human fibroblasts can express numerous regulatory molecules that influence immune function. IL-16, a ligand for CD4, is a chemoattractant molecule exp ressed by lymphocytes, eosinophils, mast cells, and lung epithelium. It app ears that the sole target for IL-16 is the CD4-bearing cell. Here we demons trate that fibroblasts from several tissues can express IL-16 mRNA and prot ein as well as IL-16-dependent chemoattractant activity. The transcript is expressed abundantly under basal culture conditions as a 2.5-kb band on Nor thern analysis, similar to that observed in lymphocytes, IL-16 protein and activity are undetectable in fibroblast cultures under these same control c onditions. However, when treated with proinflammatory cytokines such as IL- 1 beta, they express very high levels of IL-16 protein and chemoattractant activity, a substantial component of which can be blocked with IL-16-neutra lizing Abs, The amount of IL-16 protein released into the medium is 3- to 4 -fold greater, on a per cell basis, than that observed in lymphocytes. The induction of IL-16 protein by IL-1 beta can be attenuated with specific inh ibition of caspase-3, which could be detected in IL-1 beta-treated fibrobla sts. IL-1 beta also induces RANTES mRNA, protein, and activity, and most of the chemoattractant activity released from fibroblasts not derived from IL -16 can be attributed to RANTES. Human fibroblasts appear to be an importan t source of IL-16 and through expression of this molecule may have key role s In the recruitment of CD4(+) cells to sites of inflammation. IL-16 expres sion and the mechanism involved in its regulation appear to be cell type sp ecific.