title: Cultured human fibroblasts express constitutive IL-16 mRNA: cytokine induction of active IL-16 protein synthesis through a caspase-3-dependent mechanism.
abstract: Human fibroblasts can express numerous regulatory molecules that influence immune function. IL-16, a ligand for CD4, is a chemoattractant molecule expressed by lymphocytes, eosinophils, mast cells, and lung epithelium. It appears that the sole target for IL-16 is the CD4-bearing cell. Here we demonstrate that fibroblasts from several tissues can express IL-16 mRNA and protein as well as IL-16-dependent chemoattractant activity. The transcript is expressed abundantly under basal culture conditions as a 2.5-kb band on Northern analysis, similar to that observed in lymphocytes. IL-16 protein and activity are undetectable in fibroblast cultures under these same control conditions. However, when treated with proinflammatory cytokines such as IL-1beta, they express very high levels of IL-16 protein and chemoattractant activity, a substantial component of which can be blocked with IL-16-neutralizing 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-1beta can be attenuated with specific inhibition of caspase-3, which could be detected in IL-1beta-treated fibroblasts. IL-1beta 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 important source of IL-16 and through expression of this molecule may have key roles in the recruitment of CD4+ cells to sites of inflammation. IL-16 expression and the mechanism involved in its regulation appear to be cell type specific.
authors.affiliation: Division of Molecular Medicine, Department of Medicine, Albany Medical College, Center, Albany, NY 12208, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sciaky
authors.forename: W
authors.initials: W
authors.lastname: Brazer
authors.forename: D M
authors.initials: DM
authors.lastname: Center
authors.forename: W W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: T J
authors.initials: TJ
authors.lastname: Smith
mesh_terms: D053148:Caspase 3; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology*; D004789:Enzyme Activation / Q000276:immunology; D005347:Fibroblasts / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D019410:Interleukin-16 / Q000096:biosynthesis* / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology; D008222:Lymphokines / Q000494:pharmacology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D019410:Interleukin-16; D008222:Lymphokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C044162:leukoregulin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases