Cloning and characterization of an isoform of interleukin-21.
Interleukin-21 (IL-21) has pleiotropic functions on the cells, which play roles in both innate and acquired immunity, such as T cells, B cells, natural killer (NK) cells and dendritic cells. In this study we identified a novel isoform of IL-21, IL-21iso in human and mouse. IL-21iso might be an alternative splicing variant form and the C-terminal region of predicted IL-21iso amino acid sequences were different from original IL-21 in both human and mouse. In spite of the differences in C-terminal amino acid sequences, both human IL-21 and IL-21iso showed comparable proliferative effect on anti-CD40 Ab-activated primary B cells, anti-CD3 Ab-activated primary T cells and human NK cell line, NK0, and upregulated IFN-gamma production from NK0. Furthermore IL-21 and IL-21iso similarly activated STAT1 and STAT3. IL-21iso mRNA was expressed in activated T cells as well as IL-21 mRNA. However, cycloheximide treatment partially blocked the upregulation of IL-21iso mRNA in activated T cells while little affected the IL-21 mRNA expression suggesting that de novo protein synthesis is required for the full expression of IL-21iso transcript. We also show that the secretion efficiency of hIL-21iso is much lower than that of hIL-21. These results may suggest there are some different regulatory mechanisms to produce IL-21 or IL-21iso in transcriptional and secretory steps.
Department of Immunology, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan.
Mizanur
M
Rahman
Hidetoshi
H
Nara
Tadashi
T
Onoda
Akemi
A
Araki
Jun
J
Li
Tomoaki
T
Hoshino
Hironobu
H
Asao
D017398:Alternative Splicing / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000528:radiation effects; D012333:RNA, Messenger / Q000096:biosynthesis; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000098546:Interleukin-21
D000906:Antibodies; D017252:CD3 Complex; D019013:CD40 Antigens; D007378:Interleukins; D020033:Protein Isoforms; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D007371:Interferon-gamma; D000098546:Interleukin-21