IL-4 stimulates mouse macrophages to express APRIL through p38MAPK and two different downstream molecules, CREB and Stat6
Copyright policy )IL-4 stimulates mouse macrophages to express APRIL through p38MAPK and two different downstream molecules, CREB and Stat6
APRIL (a proliferation-inducing ligand) is primarily expressed by macrophages and dendritic cells, and has profound effects on B cell physiology. In this study, we investigated the role of IL-4 in APRIL expression by mouse macrophages and the signaling mechanism involved. IL-4 markedly enhanced APRIL expression in mouse macrophages at the transcriptional and protein level. The p38MAPK inhibitor SB203580 completely abolished the IL-4 effect, whereas overexpression of CREB with IL-4 augmented APRIL expression. This increase was abolished by SB203580 treatment, indicating that p38MAPK may activate CREB. Overexpression of Stat6 also augmented IL-4-induced APRIL expression; this effect was partially abolished by SB203580 but not by the Jak inhibitor AG490, indicating that Stat6 mediates IL-4-induced APRIL expression in a Jak-independent manner and that p38MAPK acts as the intermediate. Our results demonstrate that IL-4 up-regulates APRIL expression through two divergent pathways in mouse macrophages, p38MAPK-CREB and p38MAPK-Stat6.
- Kangwon National University Korea (Republic of)
- Hallym University Korea (Republic of)
- Halla University Korea (Republic of)
Mice, Inbred BALB C, Pyridines, Macrophages, Tumor Necrosis Factor Ligand Superfamily Member 13, Imidazoles, Gene Expression, Transfection, p38 Mitogen-Activated Protein Kinases, Mice, Cell Line, Tumor, Macrophages, Peritoneal, Animals, Interleukin-4, Cyclic AMP Response Element-Binding Protein, STAT6 Transcription Factor, Protein Kinase Inhibitors, Signal Transduction
Mice, Inbred BALB C, Pyridines, Macrophages, Tumor Necrosis Factor Ligand Superfamily Member 13, Imidazoles, Gene Expression, Transfection, p38 Mitogen-Activated Protein Kinases, Mice, Cell Line, Tumor, Macrophages, Peritoneal, Animals, Interleukin-4, Cyclic AMP Response Element-Binding Protein, STAT6 Transcription Factor, Protein Kinase Inhibitors, Signal Transduction
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