Interleukin-9 induces 24P3 lipocalin gene expression in murine T cell lymphomas.
Interleukin-9 (IL-9) is a Th2 cytokine whose overexpression is associated with asthma and T cell lymphomagenesis. All the IL-9 activities studied so far are mediated by a specific hemopoietin receptor that activates a Jak/STAT pathway. Searching for genes specifically modulated by IL-9, we observed that the 24P3 mRNA is strongly upregulated in BW5147 T lymphoma cells upon IL-9 stimulation. 24P3 is a member of the lipocalin family, and has been reported to bind N-formyl-Met-Leu-Phe, a potent neutrophil chemoattractant, and possibly other lipophilic mediators of inflammation. A similar 24P3 induction was observed in other T cell lymphomas (EL4 and TH201) in response to IL-9, as well as in EL4 cells stimulated with IL-6 or IL-1. By contrast, other IL-9-responsive cells such as mast cell line MC9 and B cell lymphoma A20 showed no 24P3 induction upon IL-9 stimulation. Experiments using IL-9R mutants indicated that STAT transcription factors, particularly STAT3, are involved in this process. However, 24P3 gene induction was slow, reaching a plateau from 36 to 72 hours after stimulation and was inhibited if cells were treated with cycloheximide during the first 8 hours of IL-9 stimulation, suggesting an indirect induction requiring new protein synthesis.
Ludwig Institute for Cancer Research, avenue Hippocrate, 74 B-1200 Brussels, Belgium.
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D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016906:Interleukin-9 / Q000502:physiology*; D000071068:Lipocalin-2; D054834:Lipocalins; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013953:Thymus Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D016906:Interleukin-9; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C071332:Lcn2 protein, mouse