title: A human 15-kDa IFN-induced protein induces the secretion of IFN-gamma.
abstract: A 15,000 molecular weight protein (15-kDa), induced and secreted by human PBMC after treatment with IFN-alpha or -beta, was assessed for its ability to modulate cellular function. Although it had no effect on growth or 2'5'-A synthetase activity in Daudi, U-937, or HL-60 cells, when incubated with fresh human PBMC, LPS-induced monocyte cytotoxicity against WEHI-164 target cells was augmented. This stimulation was inhibited by both an antibody against TNF-alpha and a rabbit polyclonal antiserum to the 15-kDa protein. Furthermore, when the 15-kDa protein was added to PBMC an increase in GTP cyclohydrolase I activity, as assessed by neopterin secretion, resulted. Neopterin secretion by PBMC in response to the 15-kDa was increased in a dose-responsive manner up to more than sixfold over baseline, with a 15-kDa concentration of less than 10 ng/ml effective. The 15-kDa protein also stimulated indoleamine 2,3-dioxygenase (IDO) activity in fresh, human PBMC. Induction of neopterin secretion and IDO activity was inhibited by a polyclonal antiserum to 15-kDa. LPS-induced cytotoxic activity was not augmented by 15-kDa pretreatment of purified monocytes, indicating the need for the presence of a second cell population and the indirect action of the 15-kDa on the induction of monocyte activities. When PBMC or purified CD3+ cells, but not purified CD14+ cells, were incubated with the 15-kDa protein, secretion of a factor was induced that resulted in the induction of IDO activity in PMA-differentiated THP-1 cells. An antibody to IFN-gamma, but not IFN-alpha, inhibited the induction of IDO activity by this secreted factor. In addition, antiserum to the 15-kDa blocked the secretion of IFN-gamma from the CD3+ cells. Thus, a 15-kDa product of IFN-alpha- and IFN-beta-treated monocytes and lymphocytes can stimulate secretion of IFN-gamma from CD3+ cells.
authors.affiliation: University of Wisconsin Clinical Cancer Center, Madison.
authors.forename: M
authors.initials: M
authors.lastname: Recht
authors.forename: E C
authors.initials: EC
authors.lastname: Borden
authors.forename: E
authors.initials: E
authors.lastname: Knight
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism*; D007372:Interferons / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008970:Molecular Weight; D009000:Monocytes / Q000276:immunology; D011506:Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000032:analysis
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007369:Interferon Inducers; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011506:Proteins; D007371:Interferon-gamma; D007372:Interferons; D014366:Tryptophan Oxygenase