Biological activity of interleukins-28 and -29: comparison with type I interferons.
Despite binding to receptors distinct from those of type I interferons (IFNs), human interleukins-28A, -28B and -29 (IL-28A, IL-28B and IL-29; alternatively named IFN lambda-2 {IFN-lambda2}, IFN-lambda3 and IFN-lambda1, respectively, or collectively, type III IFNs), a small family of three structurally-related cytokines, are, like IFNs, known to induce antiviral activity. To further biologically characterize IL-28A and IL-29, we compared their activities with those of IFNs in a range of human cell lines. We found that they induced antiviral activity in fewer cell lines and more weakly than IFNs; also IL-28A was less active than IL-29. Additionally, we showed IL-28A and IL-29 induced reporter genes--protein MxA promoter linked to luciferase, or interferon stimulated response element (ISRE) linked to secreted alkaline phosphatase (SEAP)--more weakly than IFN. Antiproliferative activity was induced by IFNs in most cell lines, but only in one human glioblastoma cell line, LN319, was dose-dependent IL-29-growth inhibition demonstrable. Polymerase chain reaction (PCR) quantification of messenger (m) RNA of IL-28/29 receptor subunits, IL-28Ralpha and IL-10Rbeta, indicated variable expression levels; although their expression was highest in the responsive LN319 cell line, lower but significant expression of both mRNAs was found in relatively unresponsive cell lines. In conclusion, we found IL-28A and IL-29 act similarly to IFNs, but are less effective generally and have activity in a more limited range of cell lines.
Meager
Anthony
A
Division of Immunology and Endocrinology, The National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts EN6 3QG, UK. ameager@nibsc.ac.uk
Visvalingam
Kumuthini
K
Dilger
Paula
P
Bryan
Donna
D
Wadhwa
Meenu
M
D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D007372:Interferons; D053710:Interleukin-10 Receptor beta Subunit; D007378:Interleukins / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000235:genetics; D000095022:Interferon Lambda
D016207:Cytokines; D007370:Interferon Type I; D007372:Interferons; D053710:Interleukin-10 Receptor beta Subunit; D007378:Interleukins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C081846:IL10RB protein, human; C471046:interleukin 28alpha receptor