Production of ISG-15, an interferon-inducible protein, in human corneal cells.
ISG-15, a 15-kDa protein encoded by an interferon (IFN)-stimulated gene (ISG), was produced in human corneal cell cultures prepared from donor corneas in response to each of three major types of IFN, IFN-alpha, IFN-beta, and IFN-gamma. IFN-alpha and IFN-beta induced more ISG-15 in the first 24 h of treatment than did IFN-gamma. ISG-15 was detectable within the first 3 h of treatment with either type I IFN, and production peaked at 24 h, whereas IFN-gamma did not induce detectable ISG-15 until 16 h and did not induce peak production until 48 h. Conjugates of ISG-15 to cellular proteins were detectable by Western blot beginning at 9 h after IFN-alpha or IFN-beta treatment. ISG-15 persisted in IFN-treated cells for as long as 96 h. Free, unconjugated, ISG-15 was secreted by keratocytes into cell culture medium. The extent and kinetics of production, the conjugation of ISG-15 to cell proteins, and the secretion of ISG-15 in human fibroblast derived from corneas were IFN type dependent and dose dependent.
Taylor
J L
JL
Department of Microbiology, Medical College of Wisconsin, Milwaukee 53226-0509, USA.
D'Cunha
J
J
Tom
P
P
O'Brien
W J
WJ
Borden
E C
EC
D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008970:Molecular Weight; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism; D014019:Tissue Donors; D014452:Ubiquitins / Q000031:analogs & derivatives*
D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014452:Ubiquitins; C074034:ISG15 protein, human; D016899:Interferon-beta; D007371:Interferon-gamma